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\n \n\n \n \n \n \n \n \n Adherens junction proteins on the move-From the membrane to the nucleus in intestinal diseases.\n \n \n \n \n\n\n \n Lessey, L. R.; Robinson, S. C.; Chaudhary, R.; and Daniel, J. M.\n\n\n \n\n\n\n Front Cell Dev Biol, 10: 998373. October 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Adherens$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 6 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{lessey_adherens_2022,\n\ttitle = {Adherens junction proteins on the move-{From} the membrane to the nucleus in intestinal diseases},\n\tvolume = {10},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581404/ https://www.frontiersin.org/articles/10.3389/fcell.2022.998373/full},\n\tissn = {2296-634X},\n\tdoi = {10.3389/fcell.2022.998373},\n\tabstract = {The function and structure of the mammalian epithelial cell layer is maintained by distinct intercellular adhesion complexes including adherens junctions (AJs), tight junctions, and desmosomes. The AJ is most integral for stabilizing cell-cell adhesion and conserving the structural integrity of epithelial tissues. AJs are comprised of the transmembrane protein E-cadherin and cytoplasmic catenin cofactors (α, β, γ, and p120-catenin). One organ where malfunction of AJ is a major contributor to disease states is the mammalian intestine. In the intestine, cell-cell adhesion complexes work synergistically to maintain structural integrity and homeostasis of the epithelium and prevent its malfunction. Consequently, when AJ integrity is compromised in the intestinal epithelium, the ensuing homeostatic disruption leads to diseases such as inflammatory bowel disease and colorectal carcinoma. In addition to their function at the plasma membrane, protein components of AJs also have nuclear functions and are thus implicated in regulating gene expression and intracellular signaling. Within the nucleus, AJ proteins have been shown to interact with transcription factors such as TCF/LEF and Kaiso (ZBTB33), which converge on the canonical Wnt signaling pathway. The multifaceted nature of AJ proteins highlights their complexity in modulating homeostasis and emphasizes the importance of their subcellular localization and expression in the mammalian intestine. In this review, we summarize the nuclear roles of AJ proteins in intestinal tissues; their interactions with transcription factors and how this leads to crosstalk with canonical Wnt signaling; and how nuclear AJ proteins are implicated in intestinal homeostasis and disease.},\n\tlanguage = {eng},\n\tjournal = {Front Cell Dev Biol},\n\tauthor = {Lessey, Lindyann R. and Robinson, Shaiya C. and Chaudhary, Roopali and Daniel, Juliet M.},\n\tmonth = oct,\n\tyear = {2022},\n\tpmid = {36274850},\n\tpmcid = {PMC9581404},\n\tkeywords = {Adherens Junction, catenins, colon cancer, E-cadherin, inflammatory bowel disease, Kaiso, Wnt signaling},\n\tpages = {998373},\n}\n\n

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\n \n\n \n \n \n \n \n \n Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.\n \n \n \n \n\n\n \n Hercules, S. M.; Liu, X.; Bassey-Archibong, B. B. I.; Skeete, D. H. A.; Smith Connell, S.; Daramola, A.; Banjo, A. A.; Ebughe, G.; Agan, T.; Ekanem, I.; Udosen, J.; Obiorah, C.; Ojule, A. C.; Misauno, M. A.; Dauda, A. M.; Egbujo, E. C.; Hercules, J. C.; Ansari, A.; Brain, I.; MacColl, C.; Xu, Y.; Jin, Y.; Chang, S.; Carpten, J. D.; Bédard, A.; Pond, G. R.; Blenman, K. R. M.; Manojlovic, Z.; and Daniel, J. M.\n\n\n \n\n\n\n Cancer Causes Control, 33(6): 831–841. June 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Analysis$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 9 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{hercules_analysis_2022,\n\ttitle = {Analysis of the genomic landscapes of {Barbadian} and {Nigerian} women with triple negative breast cancer},\n\tvolume = {33},\n\tissn = {1573-7225},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085672/ https://link.springer.com/article/10.1007/s10552-022-01574-x},\n\tdoi = {10.1007/s10552-022-01574-x},\n\tabstract = {PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa.\nMETHODS: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples.\nRESULTS: Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32\\% in our cohort; 63\\% in TCGA-African American; 67\\% in TCGA-European American; 63\\% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes.\nCONCLUSION: This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.},\n\tlanguage = {eng},\n\tnumber = {6},\n\tjournal = {Cancer Causes Control},\n\tauthor = {Hercules, Shawn M. and Liu, Xiyu and Bassey-Archibong, Blessing B. I. and Skeete, Desiree H. A. and Smith Connell, Suzanne and Daramola, Adetola and Banjo, Adekunbiola A. and Ebughe, Godwin and Agan, Thomas and Ekanem, Ima-Obong and Udosen, Joe and Obiorah, Christopher and Ojule, Aaron C. and Misauno, Michael A. and Dauda, Ayuba M. and Egbujo, Ejike C. and Hercules, Jevon C. and Ansari, Amna and Brain, Ian and MacColl, Christine and Xu, Yili and Jin, Yuxin and Chang, Sharon and Carpten, John D. and Bédard, André and Pond, Greg R. and Blenman, Kim R. M. and Manojlovic, Zarko and Daniel, Juliet M.},\n\tmonth = jun,\n\tyear = {2022},\n\tpmid = {35384527},\n\tpmcid = {PMC9085672},\n\tkeywords = {Barbados, Cross-Sectional Studies, Female, Genomics, Humans, Mutation, Nigeria, Triple negative breast cancer, Triple Negative Breast Neoplasms, Whole exome sequencing, Women of African ancestry},\n\tpages = {831--841},\n}\n\n

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\n \n\n \n \n \n \n \n \n Triple-negative breast cancer prevalence in Africa: a systematic review and meta-analysis.\n \n \n \n \n\n\n \n Hercules, S. M.; Alnajar, M.; Chen, C.; Mladjenovic, S. M.; Shipeolu, B. A.; Perkovic, O.; Pond, G. R.; Mbuagbaw, L.; Blenman, K. R.; and Daniel, J. M.\n\n\n \n\n\n\n BMJ Open, 12(5): e055735. May 2022.\n \n\n\n\n
\n\n\n\n \n \n $\"Triple-negative$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{hercules_triple-negative_2022,\n\ttitle = {Triple-negative breast cancer prevalence in {Africa}: a systematic review and meta-analysis},\n\tvolume = {12},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150263/ https://bmjopen.bmj.com/content/12/5/e055735.long},\n\tissn = {2044-6055},\n\tshorttitle = {Triple-negative breast cancer prevalence in {Africa}},\n\tdoi = {10.1136/bmjopen-2021-055735},\n\tabstract = {OBJECTIVE: The aggressive triple-negative breast cancer (TNBC) subtype disproportionately affects women of African ancestry across the diaspora, but its frequency across Africa has not been widely studied. This study seeks to estimate the frequency of TNBC among African populations.\nDESIGN: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.\nDATA SOURCES: PubMed, EMBASE, African Journals Online and Web of Science were searched on 25 April 2021.\nELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies that use breast cancer tissue samples from indigenous African women with sample size of eligible participants ≥40 and full receptor status for all three receptors (oestrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)) reported.\nDATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias using the modified assessment tool by Hoy et al. (2012) for prevalence studies. A random-effects meta-analysis was performed, and data were pooled using the inverse-variance method and logit transformation. Pooled frequencies were reported with 95\\% CIs calculated with the Clopper-Pearson method and heterogeneity quantified with I2 statistic. GRADE assessed the certainty of the evidence.\nRESULTS: 1808 potentially eligible studies were identified of which 67 were included in the systematic review and 60 were included in the meta- analysis. Pooled TNBC frequency across African countries represented was estimated to be 27.0\\%; 95\\% CI: 24.0\\% to 30.2\\%, I2=94\\%. Pooled TNBC frequency was highest across West Africa, 45.7\\% (n=15, 95\\% CI: 38.8\\% to 52.8\\%, I2=91\\%) and lowest in Central Africa, 14.9\\% (n=1, 95\\% CI: 8.9 \\% to 24.1\\%). Estimates for TNBC were higher for studies that used Allred guidelines for ER/PR status compared with American Society of Clinical Oncology(ASCO)/College of American Pathologists(CAP) guidelines, and for studies that used older versions of ASCO/CAP guidelines for assessing HER2 status. Certainty of evidence was assessed to be very low using GRADE approach.\nCONCLUSION: TNBC frequency was variable with the highest frequency reported in West Africa. Greater emphasis should be placed on establishing protocols for assessing receptor status due to the variability among studies.},\n\tlanguage = {eng},\n\tnumber = {5},\n\tjournal = {BMJ Open},\n\tauthor = {Hercules, Shawn M. and Alnajar, Meena and Chen, Chen and Mladjenovic, Stefan M. and Shipeolu, Bolade Ajarat and Perkovic, Olga and Pond, Greg R. and Mbuagbaw, Lawrence and Blenman, Kim Rm and Daniel, Juliet M.},\n\tmonth = may,\n\tyear = {2022},\n\tpmid = {35623750},\n\tpmcid = {PMC9150263},\n\tkeywords = {Africa, breast cancer, Female, Humans, Population Groups, Prevalence, Receptors, Estrogen, TNBC, triple negative breast cancer, Triple Negative Breast Neoplasms, women of African ancestry},\n\tpages = {e055735},\n}\n

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\n OBJECTIVE: The aggressive triple-negative breast cancer (TNBC) subtype disproportionately affects women of African ancestry across the diaspora, but its frequency across Africa has not been widely studied. This study seeks to estimate the frequency of TNBC among African populations. DESIGN: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. DATA SOURCES: PubMed, EMBASE, African Journals Online and Web of Science were searched on 25 April 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies that use breast cancer tissue samples from indigenous African women with sample size of eligible participants ≥40 and full receptor status for all three receptors (oestrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)) reported. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias using the modified assessment tool by Hoy et al. (2012) for prevalence studies. A random-effects meta-analysis was performed, and data were pooled using the inverse-variance method and logit transformation. Pooled frequencies were reported with 95% CIs calculated with the Clopper-Pearson method and heterogeneity quantified with I2 statistic. GRADE assessed the certainty of the evidence. RESULTS: 1808 potentially eligible studies were identified of which 67 were included in the systematic review and 60 were included in the meta- analysis. Pooled TNBC frequency across African countries represented was estimated to be 27.0%; 95% CI: 24.0% to 30.2%, I2=94%. Pooled TNBC frequency was highest across West Africa, 45.7% (n=15, 95% CI: 38.8% to 52.8%, I2=91%) and lowest in Central Africa, 14.9% (n=1, 95% CI: 8.9 % to 24.1%). Estimates for TNBC were higher for studies that used Allred guidelines for ER/PR status compared with American Society of Clinical Oncology(ASCO)/College of American Pathologists(CAP) guidelines, and for studies that used older versions of ASCO/CAP guidelines for assessing HER2 status. Certainty of evidence was assessed to be very low using GRADE approach. CONCLUSION: TNBC frequency was variable with the highest frequency reported in West Africa. Greater emphasis should be placed on establishing protocols for assessing receptor status due to the variability among studies.\n

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\n \n 2020\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n High triple-negative breast cancer prevalence and aggressive prognostic factors in Barbadian women with breast cancer.\n \n \n \n \n\n\n \n Hercules, S. M.; Hercules, J. C.; Ansari, A.; Date, S. A. J.; Skeete, D. H. A.; Smith Connell, S. P.; Pond, G. R.; and Daniel, J. M.\n\n\n \n\n\n\n Cancer, 126(10): 2217–2224. May 2020.\n \n\n\n\n
\n\n\n\n \n \n $\"High$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 38 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{hercules_high_2020,\n\ttitle = {High triple-negative breast cancer prevalence and aggressive prognostic factors in {Barbadian} women with breast cancer},\n\tvolume = {126},\n\turl = {https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32771},\n\tissn = {1097-0142},\n\tdoi = {10.1002/cncr.32771},\n\tabstract = {BACKGROUND: Women of African ancestry (WAA) are disproportionately affected by triple-negative breast cancer (TNBC), which remains one of the most clinically challenging breast cancer (BCa) subtypes. This study investigated the prevalence of TNBC and epidemiological trends for BCa in Barbados, a Caribbean island with a high percentage of African ancestry. METHODS: Pathology reports for all BCa cases between 2007 and 2016 were collected from the sole hospital in Barbados and reviewed. The clinicopathological data collected included age, tumor grade, lymph node status, and hormone receptor status as determined by immunohistochemistry. BCa data for non-Hispanic white (NHW) and non-Hispanic black (NHB) American populations were accessed from the Surveillance, Epidemiology, and End Results database. RESULTS: There were 1997 BCa cases in Barbados between 2007 and 2016 for an estimated incidence rate of 135.1 per 100,000 women in Barbados (standardized to the US population, where the standardized incidence rates for NHBs and NHWs were 141.4 and 152.6 per 100,000, respectively). Age-specific incidence rates in Barbados for this period were consistently higher in younger age groups (15-59 years) in comparison with NHWs and NHBs. Between 2010 and 2016 in Barbados, a TNBC prevalence of 25\\% was observed, whereas TNBC prevalences of 21\\% and 10\\% were observed in NHBs and NHWs, respectively. CONCLUSIONS: The BCa incidence was higher in younger Barbadian women than NHWs and NHBs, and the TNBC prevalence was {\\textbackslash}textasciitilde2.5 times higher than the prevalence in NHWs. This hints at a possible genetic predisposition and other socioeconomic factors that could explain the high TNBC prevalence and aggressive clinical course in WAA globally.},\n\tlanguage = {eng},\n\tnumber = {10},\n\tjournal = {Cancer},\n\tauthor = {Hercules, Shawn M. and Hercules, Jevon C. and Ansari, Amna and Date, Stephanie A. J. and Skeete, Desiree H. A. and Smith Connell, Suzanne P. and Pond, Gregory R. and Daniel, Juliet M.},\n\tmonth = may,\n\tyear = {2020},\n\tpmid = {32154924},\n\tkeywords = {Barbados, breast cancer (BCa), epidemiology, racial disparities, triple-negative breast cancer (TNBC)},\n\tpages = {2217--2224},\n}\n\n

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\n \n 2019\n \n \n (2)\n \n \n

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\n \n\n \n \n \n \n \n \n Kaiso-induced intestinal inflammation is preceded by diminished E-cadherin expression and intestinal integrity.\n \n \n \n \n\n\n \n Robinson, S. C.; Chaudhary, R.; Jiménez-Saiz, R.; Rayner, L. G. A.; Bayer, L.; Jordana, M.; and Daniel, J. M.\n\n\n \n\n\n\n PLOS ONE, 14(6): e0217220. June 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso-induced$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 15 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{robinson_kaiso-induced_2019,\n\ttitle = {Kaiso-induced intestinal inflammation is preceded by diminished {E}-cadherin expression and intestinal integrity},\n\tvolume = {14},\n\tissn = {1932-6203},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/31199830 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6568390 http://dx.plos.org/10.1371/journal.pone.0217220},\n\tdoi = {10.1371/journal.pone.0217220},\n\tabstract = {Chronic intestinal inflammation contributes to pathologies such as inflammatory bowel disease (IBD) and colon cancer. While the precise etiology remains controversial, IBD is believed to manifest as a result of various factors. We previously reported that intestinal-specific overexpression of the transcription factor Kaiso results in an intestinal inflammatory response; however, the cause of this inflammation is unknown. To elucidate the underlying mechanism(s) of the Kaiso-mediated intestinal inflammatory phenotype, we evaluated two independent transgenic mouse lines that express varying levels of Kaiso (KaisoTg). Histological analyses of KaisoTg mice revealed intestinal damage including thickening of the mucosa, intestinal "lesions" and crypt abscesses, which are reminiscent of IBD pathology. Additionally, higher Kaiso levels induced intestinal neutrophilia as early as 12 weeks, which worsened as the mice aged. Notably, the Kaiso-induced intestinal inflammation correlated with a leaky intestinal barrier and mis-regulation of E-cadherin expression and localization. Interestingly, Kaiso overexpression resulted in reduced proliferation but enhanced migration of intestinal epithelial cells prior to the onset of inflammation. Collectively, these data suggest that Kaiso plays a role in regulating intestinal epithelial cell integrity and function, dysregulation of which contributes to a chronic inflammatory phenotype as mice age.},\n\tnumber = {6},\n\tjournal = {PLOS ONE},\n\tauthor = {Robinson, Shaiya C. and Chaudhary, Roopali and Jiménez-Saiz, Rodrigo and Rayner, Lyndsay G. A. and Bayer, Luke and Jordana, Manel and Daniel, Juliet M.},\n\teditor = {Koval, Michael},\n\tmonth = jun,\n\tyear = {2019},\n\tpmid = {31199830},\n\tpages = {e0217220},\n}\n\n

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\n \n\n \n \n \n \n \n \n Dancing from bottoms up – Roles of the POZ-ZF transcription factor Kaiso in Cancer.\n \n \n \n \n\n\n \n Pierre, C. C.; Hercules, S. M.; Yates, C.; and Daniel, J. M.\n\n\n \n\n\n\n Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1871(1): 64–74. January 2019.\n \n\n\n\n
\n\n\n\n \n \n $\"Dancing$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 10 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{pierre_dancing_2019,\n\ttitle = {Dancing from bottoms up – {Roles} of the {POZ}-{ZF} transcription factor {Kaiso} in {Cancer}},\n\tvolume = {1871},\n\tissn = {0304419X},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/30419310 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6467064 https://linkinghub.elsevier.com/retrieve/pii/S0304419X18301379},\n\tdoi = {10.1016/j.bbcan.2018.10.005},\n\tabstract = {The POZ-ZF transcription factor Kaiso was discovered two decades ago as a binding partner for p120ctn. Since its discovery, roles for Kaiso in diverse biological processes (epithelial-to-mesenchymal transition, apoptosis, inflammation) and several signalling pathways (Wnt/β-catenin, TGFβ, EGFR, Notch) have emerged. While Kaiso's biological role in normal tissues has yet to be fully elucidated, Kaiso has been increasingly implicated in multiple human cancers including colon, prostate, ovarian, lung, breast and chronic myeloid leukemia. In the majority of human cancers investigated to date, high Kaiso expression correlates with aggressive tumor characteristics including proliferation and metastasis, and/or poor prognosis. More recently, interest in Kaiso stems from its apparent correlation with racial disparities in breast and prostate cancer incidence and survival outcomes in people of African Ancestry. This review discusses Kaiso's role in various cancers, and Kaiso's potential for driving racial disparities in incidence and/or outcomes in people of African ancestry.},\n\tnumber = {1},\n\tjournal = {Biochimica et Biophysica Acta (BBA) - Reviews on Cancer},\n\tauthor = {Pierre, Christina C. and Hercules, Shawn M. and Yates, Clayton and Daniel, Juliet M.},\n\tmonth = jan,\n\tyear = {2019},\n\tpmid = {30419310},\n\tkeywords = {Kaiso, Inflammation, EMT, POZ-ZF transcription factors, Racial disparities in Cancer},\n\tpages = {64--74},\n}\n\n

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\n \n\n \n \n \n \n \n \n Loss of Kaiso expression in breast cancer cells prevents intra-vascular invasion in the lung and secondary metastasis.\n \n \n \n \n\n\n \n Kwiecien, J. M.; Bassey-Archibong, B. I.; Dabrowski, W.; Rayner, L. G.; Lucas, A. R.; and Daniel, J. M.\n\n\n \n\n\n\n PLOS ONE, 12(9): e0183883. September 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Loss$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{kwiecien_loss_2017,\n\ttitle = {Loss of {Kaiso} expression in breast cancer cells prevents intra-vascular invasion in the lung and secondary metastasis},\n\tvolume = {12},\n\tissn = {1932-6203},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/28880889 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5589175 https://dx.plos.org/10.1371/journal.pone.0183883},\n\tdoi = {10.1371/journal.pone.0183883},\n\tabstract = {The metastatic activity of breast carcinomas results from complex genetic changes in epithelial tumor cells and accounts for 90\\% of deaths in affected patients. Although the invasion of the local lymphatic vessels and veins by malignant breast tumor cells and their subsequent metastasis to the lung, has been recognized, the mechanisms behind the metastatic activity of breast tumor cells to other distal organs and the pathogenesis of metastatic cancer are not well understood. In this study, we utilized derivatives of the well-established and highly metastatic triple negative breast cancer (TNBC) cell line MDA-MB-231 (MDA-231) to study breast tumor metastasis in a mouse model. These MDA-231 derivatives had depleted expression of Kaiso, a POZ-ZF transcription factor that is highly expressed in malignant, triple negative breast cancers. We previously reported that Kaiso depletion attenuates the metastasis of xenografted MDA-231 cells. Herein, we describe the pathological features of the metastatic activity of parental (Kaisopositive) versus Kaisodepleted MDA-231 cells. Both Kaisopositive and Kaisodepleted MDA-231 cells metastasized from the original tumor in the mammary fat pad to the lung. However, while Kaisopositive cells formed large masses in the lung parenchyma, invaded large pulmonary blood vessels and formed secondary metastases and large tumors in the distal organs, Kaisodepleted cells metastasized only to the lung where they formed small metastatic lesions. Importantly, intravascular invasion and secondary metastases in distal organs were not observed in mice xenografted with Kaisodepleted cells. It thus appears that the lung may constitute a barrier for less invasive breast tumors such as the Kaisodepleted TNBC cells; this barrier may limit tumor growth and prevents Kaisodepleted TNBC cells from invading the pulmonary blood vessels and forming secondary metastases in distal organs.},\n\tnumber = {9},\n\tjournal = {PLOS ONE},\n\tauthor = {Kwiecien, Jacek M. and Bassey-Archibong, Blessing I. and Dabrowski, Wojciech and Rayner, Lyndsay G. and Lucas, Alexandra R. and Daniel, Juliet M.},\n\teditor = {Ahmad, Aamir},\n\tmonth = sep,\n\tyear = {2017},\n\tpmid = {28880889},\n\tpages = {e0183883},\n}\n\n

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\n \n\n \n \n \n \n \n \n Kaiso differentially regulates components of the Notch signaling pathway in intestinal cells.\n \n \n \n \n\n\n \n Robinson, S. C.; Klobucar, K.; Pierre, C. C.; Ansari, A.; Zhenilo, S.; Prokhortchouk, E.; and Daniel, J. M.\n\n\n \n\n\n\n Cell Communication and Signaling, 15(1): 24. December 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{robinson_kaiso_2017,\n\ttitle = {Kaiso differentially regulates components of the {Notch} signaling pathway in intestinal cells},\n\tvolume = {15},\n\tissn = {1478-811X},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/28637464 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5480165 http://biosignaling.biomedcentral.com/articles/10.1186/s12964-017-0178-x},\n\tdoi = {10.1186/s12964-017-0178-x},\n\tabstract = {BACKGROUND In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso Tg ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut. However, Kaiso's precise role in Notch signaling and whether the Kaiso Tg secretory cell fate phenotype was linked to Kaiso-induced inflammation had yet to be elucidated. METHODS Intestines from 3-month old Non-transgenic and Kaiso Tg mice were "Swiss" rolled and analysed for the expression of Notch1, Dll-1, Jagged-1, and secretory cell markers by immunohistochemistry and immunofluorescence. To evaluate inflammation, morphological analyses and myeloperoxidase assays were performed on intestines from 3-month old Kaiso Tg and control mice. Notch1, Dll-1 and Jagged-1 expression were also assessed in stable Kaiso-depleted colon cancer cells and isolated intestinal epithelial cells using real time PCR and western blotting. To assess Kaiso binding to the DLL1, JAG1 and NOTCH1 promoter regions, chromatin immunoprecipitation was performed on three colon cancer cell lines. RESULTS Here we demonstrate that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulates several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. Notably, we found that in Kaiso Tg mice intestines, Notch1 and Dll-1 expression are significantly reduced while Jagged-1 expression is increased. Chromatin immunoprecipitation experiments revealed that Kaiso associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon carcinoma cell lines, suggesting that these Notch ligands are putative Kaiso target genes. CONCLUSION Here, we provide evidence that Kaiso's effects on intestinal secretory cell fates precede the development of intestinal inflammation in Kaiso Tg mice. We also demonstrate that Kaiso inhibits the expression of Dll-1, which likely contributes to the secretory cell phenotype observed in our transgenic mice. In contrast, Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression.},\n\tnumber = {1},\n\tjournal = {Cell Communication and Signaling},\n\tauthor = {Robinson, Shaiya C. and Klobucar, Kristina and Pierre, Christina C. and Ansari, Amna and Zhenilo, Svetlana and Prokhortchouk, Egor and Daniel, Juliet M.},\n\tmonth = dec,\n\tyear = {2017},\n\tpmid = {28637464},\n\tkeywords = {Kaiso, Dll-1, Intestinal cell fates, Intestinal homeostasis, Jagged-1, Notch},\n\tpages = {24},\n}\n\n

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\n BACKGROUND In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso Tg ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut. However, Kaiso's precise role in Notch signaling and whether the Kaiso Tg secretory cell fate phenotype was linked to Kaiso-induced inflammation had yet to be elucidated. METHODS Intestines from 3-month old Non-transgenic and Kaiso Tg mice were \"Swiss\" rolled and analysed for the expression of Notch1, Dll-1, Jagged-1, and secretory cell markers by immunohistochemistry and immunofluorescence. To evaluate inflammation, morphological analyses and myeloperoxidase assays were performed on intestines from 3-month old Kaiso Tg and control mice. Notch1, Dll-1 and Jagged-1 expression were also assessed in stable Kaiso-depleted colon cancer cells and isolated intestinal epithelial cells using real time PCR and western blotting. To assess Kaiso binding to the DLL1, JAG1 and NOTCH1 promoter regions, chromatin immunoprecipitation was performed on three colon cancer cell lines. RESULTS Here we demonstrate that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulates several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. Notably, we found that in Kaiso Tg mice intestines, Notch1 and Dll-1 expression are significantly reduced while Jagged-1 expression is increased. Chromatin immunoprecipitation experiments revealed that Kaiso associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon carcinoma cell lines, suggesting that these Notch ligands are putative Kaiso target genes. CONCLUSION Here, we provide evidence that Kaiso's effects on intestinal secretory cell fates precede the development of intestinal inflammation in Kaiso Tg mice. We also demonstrate that Kaiso inhibits the expression of Dll-1, which likely contributes to the secretory cell phenotype observed in our transgenic mice. In contrast, Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression.\n

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\n \n\n \n \n \n \n \n \n Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells.\n \n \n \n \n\n\n \n Bassey-Archibong, B. I; Rayner, L. G A; Hercules, S. M; Aarts, C. W; Dvorkin-Gheva, A.; Bramson, J. L; Hassell, J. A; and Daniel, J. M\n\n\n \n\n\n\n Cell Death & Disease, 8(3): e2689–e2689. March 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{bassey-archibong_kaiso_2017,\n\ttitle = {Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells},\n\tvolume = {8},\n\tissn = {2041-4889},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/28333150 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5386582 http://www.nature.com/articles/cddis201792},\n\tdoi = {10.1038/cddis.2017.92},\n\tabstract = {Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of Kaiso in the growth and survival of TNBCs. Herein, we report that Kaiso depletion attenuates TNBC cell proliferation, and delays tumor onset in mice xenografted with the aggressive MDA-231 breast tumor cells. We further demonstrate that Kaiso depletion attenuates the survival of TNBC cells and increases their propensity for apoptotic-mediated cell death. Notably, Kaiso depletion downregulates BRCA1 expression in TNBC cells expressing mutant-p53 and we found that high Kaiso and BRCA1 expression correlates with a poor overall survival in breast cancer patients. Collectively, our findings reveal a role for Kaiso in the proliferation and survival of TNBC cells, and suggest a relevant role for Kaiso in the prognosis and treatment of TNBCs.},\n\tnumber = {3},\n\tjournal = {Cell Death \\& Disease},\n\tauthor = {Bassey-Archibong, Blessing I and Rayner, Lyndsay G A and Hercules, Shawn M and Aarts, Craig W and Dvorkin-Gheva, Anna and Bramson, Jonathan L and Hassell, John A and Daniel, Juliet M},\n\tmonth = mar,\n\tyear = {2017},\n\tpmid = {28333150},\n\tpages = {e2689--e2689},\n}\n\n

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\n \n\n \n \n \n \n \n \n The POZ-ZF transcription factor Znf131 is implicated as a regulator of Kaiso-mediated biological processes.\n \n \n \n \n\n\n \n Robinson, S. C.; Donaldson-Kabwe, N. S.; Dvorkin-Gheva, A.; Longo, J.; He, L.; and Daniel, J. M.\n\n\n \n\n\n\n Biochemical and Biophysical Research Communications, 493(1): 416–421. November 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{robinson_poz-zf_2017,\n\ttitle = {The {POZ}-{ZF} transcription factor {Znf131} is implicated as a regulator of {Kaiso}-mediated biological processes},\n\tvolume = {493},\n\tissn = {0006291X},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/28882591 https://linkinghub.elsevier.com/retrieve/pii/S0006291X17317655},\n\tdoi = {10.1016/j.bbrc.2017.09.007},\n\tabstract = {Znf131 belongs to the family of POZ-ZF transcription factors, but, in contrast to most other characterized POZ-ZF proteins that function as transcriptional repressors, Znf131 acts as a transcriptional activator. Znf131 heterodimerizes with the POZ-ZF protein Kaiso, which itself represses a subset of canonical Wnt target genes, including the cell cycle regulator Cyclin D1. Herein, we report a possible role for Znf131 in Kaiso-mediated processes. Notably, we found that Znf131 associates with several Kaiso target gene promoters, including that of CCND1. ChIP analysis revealed that Znf131 indirectly associates with the CCND1 promoter in HCT116 and MCF7 cells via a region that encompasses the previously characterized +69 Kaiso Binding Site, hinting that the Znf131/Kaiso heterodimer may co-regulate Cyclin D1 expression. We also demonstrate that Kaiso inhibits Znf131 expression, raising the possibility that Kaiso and Znf131 act to fine-tune target gene expression. Together, our findings implicate Znf131 as a co-regulator of Kaiso-mediated biological processes.},\n\tnumber = {1},\n\tjournal = {Biochemical and Biophysical Research Communications},\n\tauthor = {Robinson, Shaiya C. and Donaldson-Kabwe, Nickett S. and Dvorkin-Gheva, Anna and Longo, Joseph and He, Lloyd and Daniel, Juliet M.},\n\tmonth = nov,\n\tyear = {2017},\n\tpmid = {28882591},\n\tkeywords = {Kaiso, POZ-ZF, Transcription factor, Cyclin D1, Znf131},\n\tpages = {416--421},\n}\n\n

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\n \n\n \n \n \n \n \n \n Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women.\n \n \n \n \n\n\n \n Bassey-Archibong, B. I.; Hercules, S. M.; Rayner, L. G. A.; Skeete, D. H. A.; Smith Connell, S. P.; Brain, I.; Daramola, A.; Banjo, A. A. F.; Byun, J. S.; Gardner, K.; Dushoff, J.; and Daniel, J. M.\n\n\n \n\n\n\n Cancer Causes & Control, 28(11): 1295–1304. November 2017.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{bassey-archibong_kaiso_2017-1,\n\ttitle = {Kaiso is highly expressed in {TNBC} tissues of women of {African} ancestry compared to {Caucasian} women},\n\tvolume = {28},\n\tissn = {0957-5243},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/28887687 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5681979 http://link.springer.com/10.1007/s10552-017-0955-2},\n\tdoi = {10.1007/s10552-017-0955-2},\n\tabstract = {PURPOSE Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women. METHODS Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features. RESULTS Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women. CONCLUSIONS High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.},\n\tnumber = {11},\n\tjournal = {Cancer Causes \\& Control},\n\tauthor = {Bassey-Archibong, Blessing I. and Hercules, Shawn M. and Rayner, Lyndsay G. A. and Skeete, Desiree H. A. and Smith Connell, Suzanne P. and Brain, Ian and Daramola, Adetola and Banjo, Adekunbiola A. F. and Byun, Jung S. and Gardner, Kevin and Dushoff, Jonathan and Daniel, Juliet M.},\n\tmonth = nov,\n\tyear = {2017},\n\tpmid = {28887687},\n\tkeywords = {Kaiso, Breast cancer racial disparity, TNBC, Women of African ancestry},\n\tpages = {1295--1304},\n}\n\n

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\n \n 2016\n \n \n (2)\n \n \n

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\n \n\n \n \n \n \n \n \n Kaiso depletion attenuates transforming growth factor-β signaling and metastatic activity of triple-negative breast cancer cells.\n \n \n \n \n\n\n \n Bassey-Archibong, B I; Kwiecien, J M; Milosavljevic, S B; Hallett, R M; Rayner, L G A; Erb, M J; Crawford-Brown, C J; Stephenson, K B; Bédard, P.; Hassell, J A; and Daniel, J M\n\n\n \n\n\n\n Oncogenesis, 5(3): e208–e208. March 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{bassey-archibong_kaiso_2016,\n\ttitle = {Kaiso depletion attenuates transforming growth factor-β signaling and metastatic activity of triple-negative breast cancer cells},\n\tvolume = {5},\n\tissn = {2157-9024},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/26999717 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4815049 http://www.nature.com/articles/oncsis201617},\n\tdoi = {10.1038/oncsis.2016.17},\n\tabstract = {Triple-negative breast cancers (TNBCs) represent a subset of breast tumors that are highly aggressive and metastatic, and are responsible for a disproportionate number of breast cancer-related deaths. Several studies have postulated a role for the epithelial-to-mesenchymal transition (EMT) program in the increased aggressiveness and metastatic propensity of TNBCs. Although EMT is essential for early vertebrate development and wound healing, it is frequently co-opted by cancer cells during tumorigenesis. One prominent signaling pathway involved in EMT is the transforming growth factor-β (TGFβ) pathway. In this study, we report that the novel POZ-ZF transcription factor Kaiso is highly expressed in TNBCs and correlates with a shorter metastasis-free survival. Notably, Kaiso expression is induced by the TGFβ pathway and silencing Kaiso expression in the highly invasive breast cancer cell lines, MDA-MB-231 (hereafter MDA-231) and Hs578T, attenuated the expression of several EMT-associated proteins (Vimentin, Slug and ZEB1), abrogated TGFβ signaling and TGFβ-dependent EMT. Moreover, Kaiso depletion attenuated the metastasis of TNBC cells (MDA-231 and Hs578T) in a mouse model. Although high Kaiso and high TGFβR1 expression is associated with poor overall survival in breast cancer patients, overexpression of a kinase-active TGFβR1 in the Kaiso-depleted cells was insufficient to restore the metastatic potential of these cells, suggesting that Kaiso is a key downstream component of TGFβ-mediated pro-metastatic responses. Collectively, these findings suggest a critical role for Kaiso in TGFβ signaling and the metastasis of TNBCs.},\n\tnumber = {3},\n\tjournal = {Oncogenesis},\n\tauthor = {Bassey-Archibong, B I and Kwiecien, J M and Milosavljevic, S B and Hallett, R M and Rayner, L G A and Erb, M J and Crawford-Brown, C J and Stephenson, K B and Bédard, P-A and Hassell, J A and Daniel, J M},\n\tmonth = mar,\n\tyear = {2016},\n\tpmid = {26999717},\n\tpages = {e208--e208},\n}\n\n

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\n \n\n \n \n \n \n \n \n Kaiso, a transcriptional repressor, promotes cell migration and invasion of prostate cancer cells through regulation of miR-31 expression.\n \n \n \n \n\n\n \n Wang, H.; Liu, W.; Black, S.; Turner, O.; Daniel, J. M.; Dean-Colomb, W.; He, Q. P.; Davis, M.; and Yates, C.\n\n\n \n\n\n\n Oncotarget, 7(5): 5677–89. February 2016.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso,$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{wang_kaiso_2016,\n\ttitle = {Kaiso, a transcriptional repressor, promotes cell migration and invasion of prostate cancer cells through regulation of {miR}-31 expression},\n\tvolume = {7},\n\tissn = {1949-2553},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/26734997 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4868713 http://www.oncotarget.com/fulltext/6801},\n\tdoi = {10.18632/oncotarget.6801},\n\tabstract = {Kaiso, a member of the BTB/POZ zinc finger protein family, functions as a transcriptional repressor by binding to sequence-specific Kaiso binding sites or to methyl-CpG dinucleotides. Previously, we demonstrated that Kaiso overexpression and nuclear localization correlated with the progression of prostate cancer (PCa). Therefore, our objective was to explore the molecular mechanisms underlying Kaiso-mediated PCa progression. Comparative analysis of miRNA arrays revealed that 13 miRNAs were significantly altered ({\\textbackslash}textbackslashtextgreater 1.5 fold, p {\\textbackslash}textbackslashtextless 0.05) in sh-Kaiso PC-3 compared to sh-Scr control cells. Real-time PCR validated that three miRNAs (9, 31, 636) were increased in sh-Kaiso cells similar to cells treated with 5-aza-2'-deoxycytidine. miR-31 expression negatively correlated with Kaiso expression and with methylation of the miR-31 promoter in a panel of PCa cell lines. ChIP assays revealed that Kaiso binds directly to the miR-31 promoter in a methylation-dependent manner. Over-expression of miR-31 decreased cell proliferation, migration and invasiveness of PC-3 cells, whereas cells transfected with anti-miR-31 restored proliferation, migration and invasiveness of sh-Kaiso PC-3 cells. In PCa patients, Kaiso high/miR-31 low expression correlated with worse overall survival relative to each marker individually. In conclusion, these results demonstrate that Kaiso promotes cell migration and invasiveness through regulation of miR-31 expression.},\n\tnumber = {5},\n\tjournal = {Oncotarget},\n\tauthor = {Wang, Honghe and Liu, Wei and Black, ShaNekkia and Turner, Omari and Daniel, Juliet M. and Dean-Colomb, Windy and He, Qinghua P. and Davis, Melissa and Yates, Clayton},\n\tmonth = feb,\n\tyear = {2016},\n\tpmid = {26734997},\n\tkeywords = {Kaiso, DNA methylation, miRNA, prostate cancer},\n\tpages = {5677--89},\n}\n\n

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\n \n\n \n \n \n \n \n \n Methylation-dependent regulation of hypoxia inducible factor-1 alpha gene expression by the transcription factor Kaiso.\n \n \n \n \n\n\n \n Pierre, C. C.; Longo, J.; Bassey-Archibong, B. I.; Hallett, R. M.; Milosavljevic, S.; Beatty, L.; Hassell, J. A.; and Daniel, J. M.\n\n\n \n\n\n\n Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1849(12): 1432–1441. December 2015.\n \n\n\n\n
\n\n\n\n \n \n $\"Methylation-dependent$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{pierre_methylation-dependent_2015,\n\ttitle = {Methylation-dependent regulation of hypoxia inducible factor-1 alpha gene expression by the transcription factor {Kaiso}},\n\tvolume = {1849},\n\tissn = {18749399},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/26514431 https://linkinghub.elsevier.com/retrieve/pii/S1874939915002308},\n\tdoi = {10.1016/j.bbagrm.2015.10.018},\n\tabstract = {Low oxygen tension (hypoxia) is a common characteristic of solid tumors and strongly correlates with poor prognosis and resistance to treatment. In response to hypoxia, cells initiate a cascade of transcriptional events regulated by the hypoxia inducible factor-1 (HIF-1) heterodimer. Since the oxygen-sensitive HIF-1α subunit is stabilized during hypoxia, it functions as the regulatory subunit of the protein. To date, while the mechanisms governing HIF-1α protein stabilization and function have been well studied, those governing HIF1A gene expression are not fully understood. However, recent studies have suggested that methylation of a HIF-1 binding site in the HIF1A promoter prevents its autoregulation. Here we report that the POZ-ZF transcription factor Kaiso modulates HIF1A gene expression by binding to the methylated HIF1A promoter in a region proximal to the autoregulatory HIF-1 binding site. Interestingly, Kaiso's regulation of HIF1A occurs primarily during hypoxia, which is consistent with the finding that Kaiso protein levels peak after 4 h of hypoxic incubation and return to normoxic levels after 24 h. Our data thus support a role for Kaiso in fine-tuning HIF1A gene expression after extended periods of hypoxia.},\n\tnumber = {12},\n\tjournal = {Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms},\n\tauthor = {Pierre, Christina C. and Longo, Joseph and Bassey-Archibong, Blessing I. and Hallett, Robin M. and Milosavljevic, Snezana and Beatty, Laura and Hassell, John A. and Daniel, Juliet M.},\n\tmonth = dec,\n\tyear = {2015},\n\tpmid = {26514431},\n\tkeywords = {Kaiso, POZ-ZF, DNA methylation, HIF-1, Hypoxia, Transcription factor, Transcription regulation},\n\tpages = {1432--1441},\n}\n\n

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\n \n\n \n \n \n \n \n \n Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in ApcMin/+ mice.\n \n \n \n \n\n\n \n Pierre, C. C.; Longo, J.; Mavor, M.; Milosavljevic, S. B.; Chaudhary, R.; Gilbreath, E.; Yates, C.; and Daniel, J. M.\n\n\n \n\n\n\n Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1852(9): 1846–1855. September 2015.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n

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@article{pierre_kaiso_2015,\n\ttitle = {Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in {ApcMin}/+ mice},\n\tvolume = {1852},\n\tissn = {09254439},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/26073433 https://linkinghub.elsevier.com/retrieve/pii/S0925443915001775},\n\tdoi = {10.1016/j.bbadis.2015.06.011},\n\tabstract = {Constitutive Wnt/β-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/β-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine.},\n\tnumber = {9},\n\tjournal = {Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease},\n\tauthor = {Pierre, Christina C. and Longo, Joseph and Mavor, Meaghan and Milosavljevic, Snezana B. and Chaudhary, Roopali and Gilbreath, Ebony and Yates, Clayton and Daniel, Juliet M.},\n\tmonth = sep,\n\tyear = {2015},\n\tpmid = {26073433},\n\tkeywords = {Kaiso, Inflammation, Tumorigenesis, Wnt, Apc},\n\tpages = {1846--1855},\n}\n\n

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\n \n 2013\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n The POZ-ZF Transcription Factor Kaiso (ZBTB33) Induces Inflammation and Progenitor Cell Differentiation in the Murine Intestine.\n \n \n \n \n\n\n \n Chaudhary, R.; Pierre, C. C.; Nanan, K.; Wojtal, D.; Morone, S.; Pinelli, C.; Wood, G. A.; Robine, S.; and Daniel, J. M.\n\n\n \n\n\n\n PLoS ONE, 8(9): e74160. September 2013.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{chaudhary_poz-zf_2013,\n\ttitle = {The {POZ}-{ZF} {Transcription} {Factor} {Kaiso} ({ZBTB33}) {Induces} {Inflammation} and {Progenitor} {Cell} {Differentiation} in the {Murine} {Intestine}},\n\tvolume = {8},\n\tissn = {1932-6203},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/24040197 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3764064 http://dx.plos.org/10.1371/journal.pone.0074160},\n\tdoi = {10.1371/journal.pone.0074160},\n\tabstract = {Since its discovery, several studies have implicated the POZ-ZF protein Kaiso in both developmental and tumorigenic processes. However, most of the information regarding Kaiso's function to date has been gleaned from studies in Xenopus laevis embryos and mammalian cultured cells. To examine Kaiso's role in a relevant, mammalian organ-specific context, we generated and characterized a Kaiso transgenic mouse expressing a murine Kaiso transgene under the control of the intestine-specific villin promoter. Kaiso transgenic mice were viable and fertile but pathological examination of the small intestine revealed distinct morphological changes. Kaiso transgenics (Kaiso(Tg/+)) exhibited a crypt expansion phenotype that was accompanied by increased differentiation of epithelial progenitor cells into secretory cell lineages; this was evidenced by increased cell populations expressing Goblet, Paneth and enteroendocrine markers. Paradoxically however, enhanced differentiation in Kaiso(Tg/+) was accompanied by reduced proliferation, a phenotype reminiscent of Notch inhibition. Indeed, expression of the Notch signalling target HES-1 was decreased in Kaiso(Tg/+) animals. Finally, our Kaiso transgenics exhibited several hallmarks of inflammation, including increased neutrophil infiltration and activation, villi fusion and crypt hyperplasia. Interestingly, the Kaiso binding partner and emerging anti-inflammatory mediator p120(ctn) is recruited to the nucleus in Kaiso(Tg/+) mice intestinal cells suggesting that Kaiso may elicit inflammation by antagonizing p120(ctn) function.},\n\tnumber = {9},\n\tjournal = {PLoS ONE},\n\tauthor = {Chaudhary, Roopali and Pierre, Christina C. and Nanan, Kyster and Wojtal, Daria and Morone, Simona and Pinelli, Christopher and Wood, Geoffrey A. and Robine, Sylvie and Daniel, Juliet M.},\n\teditor = {Defossez, Pierre-Antoine},\n\tmonth = sep,\n\tyear = {2013},\n\tpmid = {24040197},\n\tpages = {e74160},\n}\n\n

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\n \n 2012\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n Kaiso Represses the Cell Cycle Gene cyclin D1 via Sequence-Specific and Methyl-CpG-Dependent Mechanisms.\n \n \n \n \n\n\n \n Donaldson, N. S.; Pierre, C. C.; Anstey, M. I.; Robinson, S. C.; Weerawardane, S. M.; and Daniel, J. M.\n\n\n \n\n\n\n PLoS ONE, 7(11): e50398. November 2012.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{donaldson_kaiso_2012,\n\ttitle = {Kaiso {Represses} the {Cell} {Cycle} {Gene} cyclin {D1} via {Sequence}-{Specific} and {Methyl}-{CpG}-{Dependent} {Mechanisms}},\n\tvolume = {7},\n\tissn = {1932-6203},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/23226276 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3511522 https://dx.plos.org/10.1371/journal.pone.0050398},\n\tdoi = {10.1371/journal.pone.0050398},\n\tabstract = {Kaiso is the first member of the POZ family of zinc finger transcription factors reported to bind DNA with dual-specificity in both a sequence- and methyl-CpG-specific manner. Here, we report that Kaiso associates with and regulates the cyclin D1 promoter via the consensus Kaiso binding site (KBS), and also via methylated CpG-dinucleotides. The methyl-CpG sites appear critical for Kaiso binding to the cyclin D1 promoter, while a core KBS in close proximity to the methyl-CpGs appears to stabilize Kaiso DNA binding. Kaiso's binding to both sites was demonstrated in vitro using electrophoretic mobility shift assays (EMSA) and in vivo using Chromatin immunoprecipitation (ChIP). To elucidate the functional relevance of Kaiso's binding to the cyclin D1 promoter, we assessed Kaiso overexpression effects on a minimal cyclin D1 promoter-reporter that contains both KBS and CpG sites. Kaiso repressed this minimal cyclin D1 promoter-reporter in a dose-dependent manner and transcriptional repression occurred in a KBS-specific and methyl-CpG-dependent manner. Collectively our data validates cyclin D1 as a Kaiso target gene and demonstrates a mechanism for Kaiso binding and regulation of the cyclin D1 promoter. Our data also provides a mechanistic basis for how Kaiso may regulate other target genes whose promoters possess both KBS and methyl-CpG sites.},\n\tnumber = {11},\n\tjournal = {PLoS ONE},\n\tauthor = {Donaldson, Nickett S. and Pierre, Christina C. and Anstey, Michelle I. and Robinson, Shaiya C. and Weerawardane, Sonali M. and Daniel, Juliet M.},\n\teditor = {Defossez, Pierre-Antoine},\n\tmonth = nov,\n\tyear = {2012},\n\tpmid = {23226276},\n\tpages = {e50398},\n}\n\n

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\n \n 2010\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n Kaiso regulates Znf131-mediated transcriptional activation.\n \n \n \n \n\n\n \n Donaldson, N. S.; Nordgaard, C. L.; Pierre, C. C.; Kelly, K. F.; Robinson, S. C.; Swystun, L.; Henriquez, R.; Graham, M.; and Daniel, J. M.\n\n\n \n\n\n\n Experimental Cell Research, 316(10): 1692–1705. June 2010.\n \n\n\n\n
\n\n\n\n \n \n $\"Kaiso$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{donaldson_kaiso_2010,\n\ttitle = {Kaiso regulates {Znf131}-mediated transcriptional activation},\n\tvolume = {316},\n\tissn = {00144827},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/20303951 https://linkinghub.elsevier.com/retrieve/pii/S0014482710001187},\n\tdoi = {10.1016/j.yexcr.2010.03.011},\n\tabstract = {Kaiso is a dual-specificity POZ-ZF transcription factor that regulates gene expression by binding to sequence-specific Kaiso binding sites (KBS) or methyl-CpG dinucleotide pairs. Kaiso was first identified as a binding partner for the epithelial cell adhesion regulator p120(ctn). The p120(ctn)/Kaiso interaction is reminiscent of the beta-catenin/TCF interaction and several studies have suggested that Kaiso is a negative regulator of the Wnt/beta-catenin TCF signaling pathway. To gain further insight into Kaiso's function, we performed a yeast two-hybrid screen using the Kaiso POZ domain as bait. This screen identified the POZ-ZF protein, Znf131, as a Kaiso-specific binding partner. GST pull-down assays confirmed that the interaction is mediated via the POZ domain of each protein, and co-immunoprecipitation experiments further supported an in vivo Kaiso-Znf131 interaction. Using a Cyclic Amplification and Selection of Targets (CAST) approach, we identified the 12-base pair DNA palindrome sequence GTCGCR-(X)(n)-YGCGAC as a potential Znf131 binding element (ZBE). In vitro studies using electrophoretic mobility shift assay (EMSA) demonstrated that Znf131 binds the ZBE via its zinc finger domain. Znf131 DNA-binding specificity was confirmed using competition assays and ZBE mutational analyses. An artificial promoter-reporter construct containing four tandem copies of the ZBE was constructed and used to assess Znf131 transcriptional properties. We observed dose-dependent transcriptional activation of this artificial promoter-reporter by Znf131 in both epithelial and fibroblast cells, suggesting that Znf131 is a transcriptional activator. Kaiso overexpression significantly decreased the Znf131-mediated transcriptional activation, and interestingly, co-expression of the Kaiso-specific interaction partner p120(ctn) relieved Kaiso's inhibition of Znf131-mediated transcriptional activation. These findings indicate that Znf131 is a transcriptional activator, a less common function of POZ-ZF proteins, that is negatively regulated by its heterodimerization partner Kaiso.},\n\tnumber = {10},\n\tjournal = {Experimental Cell Research},\n\tauthor = {Donaldson, Nickett S. and Nordgaard, Curtis L. and Pierre, Christina C. and Kelly, Kevin F. and Robinson, Shaiya C. and Swystun, Laura and Henriquez, Roberto and Graham, Monica and Daniel, Juliet M.},\n\tmonth = jun,\n\tyear = {2010},\n\tpmid = {20303951},\n\tpages = {1692--1705},\n}\n\n

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\n\n\n

\n Kaiso is a dual-specificity POZ-ZF transcription factor that regulates gene expression by binding to sequence-specific Kaiso binding sites (KBS) or methyl-CpG dinucleotide pairs. Kaiso was first identified as a binding partner for the epithelial cell adhesion regulator p120(ctn). The p120(ctn)/Kaiso interaction is reminiscent of the beta-catenin/TCF interaction and several studies have suggested that Kaiso is a negative regulator of the Wnt/beta-catenin TCF signaling pathway. To gain further insight into Kaiso's function, we performed a yeast two-hybrid screen using the Kaiso POZ domain as bait. This screen identified the POZ-ZF protein, Znf131, as a Kaiso-specific binding partner. GST pull-down assays confirmed that the interaction is mediated via the POZ domain of each protein, and co-immunoprecipitation experiments further supported an in vivo Kaiso-Znf131 interaction. Using a Cyclic Amplification and Selection of Targets (CAST) approach, we identified the 12-base pair DNA palindrome sequence GTCGCR-(X)(n)-YGCGAC as a potential Znf131 binding element (ZBE). In vitro studies using electrophoretic mobility shift assay (EMSA) demonstrated that Znf131 binds the ZBE via its zinc finger domain. Znf131 DNA-binding specificity was confirmed using competition assays and ZBE mutational analyses. An artificial promoter-reporter construct containing four tandem copies of the ZBE was constructed and used to assess Znf131 transcriptional properties. We observed dose-dependent transcriptional activation of this artificial promoter-reporter by Znf131 in both epithelial and fibroblast cells, suggesting that Znf131 is a transcriptional activator. Kaiso overexpression significantly decreased the Znf131-mediated transcriptional activation, and interestingly, co-expression of the Kaiso-specific interaction partner p120(ctn) relieved Kaiso's inhibition of Znf131-mediated transcriptional activation. These findings indicate that Znf131 is a transcriptional activator, a less common function of POZ-ZF proteins, that is negatively regulated by its heterodimerization partner Kaiso.\n

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\n \n 2007\n \n \n (2)\n \n \n

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\n \n\n \n \n \n \n \n \n Nuclear trafficking of the POZ-ZF protein Znf131.\n \n \n \n \n\n\n \n Donaldson, N. S.; Daniel, Y.; Kelly, K. F.; Graham, M.; and Daniel, J. M.\n\n\n \n\n\n\n Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1773(4): 546–555. April 2007.\n \n\n\n\n
\n\n\n\n \n \n $\"Nuclear$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{donaldson_nuclear_2007,\n\ttitle = {Nuclear trafficking of the {POZ}-{ZF} protein {Znf131}},\n\tvolume = {1773},\n\tissn = {01674889},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/17306895 https://linkinghub.elsevier.com/retrieve/pii/S016748890600454X},\n\tdoi = {10.1016/j.bbamcr.2006.12.005},\n\tabstract = {Znf131 is a member of the BTB/POZ family of transcription factors with roles in development and carcinogenesis. Like many members of this protein family, Znf131 displays robust nuclear localization in cultured cells, but the mechanism(s) of Znf131 nuclear trafficking is unknown. Here, we report the mechanism of Znf131 nuclear localization. Visual inspection of the Znf131 amino acid sequence revealed three basic regions (BR-1, -2 and -3) with the potential to serve as nuclear localization signals (NLS). Of the three basic regions, only BR-1 functioned independently to efficiently target heterologous beta-gal-GFP fusion proteins to HeLa cell nuclei. However, a Znf131 truncation mutant containing BR-2 and BR-3 efficiently targeted heterologous beta-gal-GFP fusion proteins to HeLa cell nuclei. Mutational analysis of full-length GFP-tagged Znf131 revealed that loss of any one BR alone did not prevent Znf131 nuclear localization. This apparent redundancy in NLS activity was due to the fact that intact BR-1 or BR-2 alone could target full-length Znf131 to nuclei. Consequently, simultaneous mutation of BR-1 and BR-2 abolished full-length Znf131 nuclear localization. Therefore, BR-1 and BR-2 are functional NLSs for Znf131 and as such are designated NLS-1 and NLS-2. Finally, wild type Znf131, and not a Znf131 NLS-defective mutant (NLS-1m/NLS-2m) interacted preferentially with the nuclear import receptor Importin-alpha3 in vitro.},\n\tnumber = {4},\n\tjournal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},\n\tauthor = {Donaldson, Nickett S. and Daniel, Yasmin and Kelly, Kevin F. and Graham, Monica and Daniel, Juliet M.},\n\tmonth = apr,\n\tyear = {2007},\n\tpmid = {17306895},\n\tpages = {546--555},\n}\n\n

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\n \n\n \n \n \n \n \n \n Dancing in and out of the nucleus: p120ctn and the transcription factor Kaiso.\n \n \n \n \n\n\n \n Daniel, J. M.\n\n\n \n\n\n\n Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1773(1): 59–68. January 2007.\n \n\n\n\n
\n\n\n\n \n \n $\"Dancing$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 4 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{daniel_dancing_2007,\n\ttitle = {Dancing in and out of the nucleus: p120ctn and the transcription factor {Kaiso}},\n\tvolume = {1773},\n\tissn = {01674889},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/17050009 https://linkinghub.elsevier.com/retrieve/pii/S0167488906002734},\n\tdoi = {10.1016/j.bbamcr.2006.08.052},\n\tabstract = {The catenin p120 (hereafter p120(ctn)) was first identified as a Src kinase substrate and subsequently characterized as an Armadillo catenin member of the cell-cell adhesion cadherin-catenin complex. In the past decade, many studies have revealed roles for p120(ctn) in regulating Rho family GTPase activity and E-cadherin stability and turnover, events that occur predominantly at the plasma membrane or in the cytoplasm. However, the recent discovery of the nuclear BTB/POZ-ZF transcription factor Kaiso as a p120(ctn) binding partner, coupled with the detection of p120(ctn) in the nucleus of some cell lines and tumor tissues, suggested that like the classical beta-catenin, p120(ctn) undergoes nucleocytoplasmic trafficking and regulates gene expression. Indeed, p120(ctn) has a classic nuclear localization signal and does traffic to the nucleus. Moreover, nuclear p120(ctn) regulates Kaiso DNA-binding and transcriptional activity, similar to beta-catenin's modulation of TCF/LEF transcription activity. However unlike beta-catenin, p120(ctn) does not appear to be a transcriptional activator. Hence it remains to be determined whether the sole role of nuclear p120(ctn) is regulation of Kaiso or whether p120(ctn) binds and regulates other transcription factors or nuclear proteins.},\n\tnumber = {1},\n\tjournal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},\n\tauthor = {Daniel, Juliet M.},\n\tmonth = jan,\n\tyear = {2007},\n\tpmid = {17050009},\n\tpages = {59--68},\n}\n\n

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\n \n 2006\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n POZ for effect – POZ-ZF transcription factors in cancer and development.\n \n \n \n \n\n\n \n Kelly, K. F.; and Daniel, J. M.\n\n\n \n\n\n\n Trends in Cell Biology, 16(11): 578–587. November 2006.\n \n\n\n\n
\n\n\n\n \n \n $\"POZ$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{kelly_poz_2006,\n\ttitle = {{POZ} for effect – {POZ}-{ZF} transcription factors in cancer and development},\n\tvolume = {16},\n\tissn = {09628924},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/16996269 https://linkinghub.elsevier.com/retrieve/pii/S096289240600239X},\n\tdoi = {10.1016/j.tcb.2006.09.003},\n\tabstract = {The BTB/POZ-ZF [Broad complex, Tramtrack, Bric à brac (BTB) or poxvirus and zinc finger (POZ)-zinc finger] protein family comprises a diverse group of transcription factors. POZ-ZF proteins have been implicated in many biological processes, including B cell fate determination, DNA damage responses, cell cycle progression and a multitude of developmental events, including gastrulation, limb formation and hematopoietic stem cell fate determination. Consequently, dysfunction of vertebrate POZ-ZF proteins, such as promyelocytic leukemia zinc finger (PLZF), B cell lymphoma 6 (Bcl-6), hypermethylated in cancer 1 (HIC-1), Kaiso, ZBTB7 and Fanconi anemia zinc finger (FAZF), has been linked directly or indirectly to tumorigenesis and developmental disorders. Here, we discuss recent advances in the POZ-ZF field and the implications for the design of future studies to elucidate the biological roles of these unique transcription factors.},\n\tnumber = {11},\n\tjournal = {Trends in Cell Biology},\n\tauthor = {Kelly, Kevin F. and Daniel, Juliet M.},\n\tmonth = nov,\n\tyear = {2006},\n\tpmid = {16996269},\n\tpages = {578--587},\n}\n\n

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\n \n 2005\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the β-catenin/TCF target gene matrilysin.\n \n \n \n \n\n\n \n Spring, C. M.; Kelly, K. F.; O'Kelly, I.; Graham, M.; Crawford, H. C.; and Daniel, J. M.\n\n\n \n\n\n\n Experimental Cell Research, 305(2): 253–265. May 2005.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{spring_catenin_2005,\n\ttitle = {The catenin p120ctn inhibits {Kaiso}-mediated transcriptional repression of the β-catenin/{TCF} target gene matrilysin},\n\tvolume = {305},\n\tissn = {00144827},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/15817151 https://linkinghub.elsevier.com/retrieve/pii/S0014482705000145},\n\tdoi = {10.1016/j.yexcr.2005.01.007},\n\tabstract = {The POZ-zinc finger transcription factor Kaiso was first identified as a specific binding partner for the Armadillo catenin and cell adhesion cofactor, p120ctn. Kaiso is a unique POZ protein with bi-modal DNA-binding properties; it associates with a sequence-specific DNA consensus Kaiso binding site (KBS) or methylated CpG dinucleotides, and regulates transcription of artificial promoters containing either site. Interestingly, the promoter of the Wnt/beta-catenin/TCF target gene matrilysin possesses two conserved copies of the KBS, which suggested that Kaiso might regulate matrilysin expression. In this study, we demonstrate using chromatin immunoprecipitation analysis that Kaiso associates with the matrilysin promoter in vivo. Minimal promoter assays further confirmed that Kaiso specifically repressed transcription of the matrilysin promoter; mutation of the KBS element or RNAi-mediated depletion of Kaiso abrogated this effect. More importantly, Kaiso blocked beta-catenin-mediated activation of the matrilysin promoter. Consistent with our previous findings, both Kaiso-DNA binding and Kaiso-mediated transcriptional repression of the matrilysin promoter were inhibited by overexpression of wild-type p120ctn, but not by a p120ctn mutant exhibiting impaired nuclear import. Collectively, our data establish Kaiso as a sequence-specific transcriptional repressor of the matrilysin promoter, and suggest that p120ctn and beta-catenin act in a synergistic manner, via distinct mechanisms, to activate matrilysin expression.},\n\tnumber = {2},\n\tjournal = {Experimental Cell Research},\n\tauthor = {Spring, Christopher M. and Kelly, Kevin F. and O'Kelly, Ita and Graham, Monica and Crawford, Howard C. and Daniel, Juliet M.},\n\tmonth = may,\n\tyear = {2005},\n\tpmid = {15817151},\n\tpages = {253--265},\n}\n\n

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\n \n 2004\n \n \n (4)\n \n \n

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\n \n\n \n \n \n \n \n \n Nuclear import of the BTB/POZ transcriptional regulator Kaiso.\n \n \n \n \n\n\n \n Kelly, K. F.; Otchere, A. A; Graham, M.; and Daniel, J. M\n\n\n \n\n\n\n Journal of Cell Science, 117(25): 6143–6152. December 2004.\n \n\n\n\n
\n\n\n\n \n \n $\"Nuclear$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{kelly_nuclear_2004,\n\ttitle = {Nuclear import of the {BTB}/{POZ} transcriptional regulator {Kaiso}},\n\tvolume = {117},\n\tissn = {0021-9533},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/15564377 http://jcs.biologists.org/cgi/doi/10.1242/jcs.01541},\n\tdoi = {10.1242/jcs.01541},\n\tabstract = {Kaiso is a BTB/POZ transcription factor that functions in vitro as a transcriptional repressor of the matrix metalloproteinase gene matrilysin and the non-canonical Wnt signaling gene Wnt-11, and as an activator of the acetylcholine-receptor-clustering gene rapsyn. Similar to other BTB/POZ proteins (e.g. Bcl-6, PLZF, HIC-1), endogenous Kaiso localizes predominantly to the nuclei of mammalian cells. To date, however, the mechanism of nuclear import for most POZ transcription factors, including Kaiso, remain unknown. Here, we report the identification and characterization of a highly basic nuclear localization signal (NLS) in Kaiso. The functionality of this NLS was verified by its ability to target a heterologous beta-galactosidase/green-fluorescent-protein fusion protein to nuclei. The mutation of one positively charged lysine to alanine in the NLS of full-length Kaiso significantly inhibited its nuclear localization in various cell types. In addition, wild-type Kaiso, but not NLS-defective Kaiso, interacted directly with the nuclear import receptor Importin-alpha2 both in vitro and in vivo. Finally, minimal promoter assays using a sequence-specific Kaiso-binding-site fusion with luciferase as reporter demonstrated that the identified NLS was crucial for Kaiso-mediated transcriptional repression. The identification of a Kaiso NLS thus clarifies the mechanism by which Kaiso translocates to the nucleus to regulate transcription of genes with diverse roles in cell growth and development.},\n\tnumber = {25},\n\tjournal = {Journal of Cell Science},\n\tauthor = {Kelly, K. F. and Otchere, Abena A and Graham, Monica and Daniel, Juliet M},\n\tmonth = dec,\n\tyear = {2004},\n\tpmid = {15564377},\n\tpages = {6143--6152},\n}\n\n

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\n \n\n \n \n \n \n \n \n Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin.\n \n \n \n \n\n\n \n Kim, S. W.; Park, J.; Spring, C. M.; Sater, A. K.; Ji, H.; Otchere, A. A.; Daniel, J. M.; and McCrea, P. D.\n\n\n \n\n\n\n Nature Cell Biology, 6(12): 1212–1220. December 2004.\n \n\n\n\n
\n\n\n\n \n \n $\"Non-canonical$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{kim_non-canonical_2004,\n\ttitle = {Non-canonical {Wnt} signals are modulated by the {Kaiso} transcriptional repressor and p120-catenin},\n\tvolume = {6},\n\tissn = {1465-7392},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/15543138 http://www.nature.com/articles/ncb1191},\n\tdoi = {10.1038/ncb1191},\n\tabstract = {Gastrulation movements are critical for establishing the three principal germ layers and the basic architecture of vertebrate embryos. Although the individual molecules and pathways involved are not clearly understood, non-canonical Wnt signals are known to participate in developmental processes, including planar cell polarity and directed cell rearrangements. Here we demonstrate that the dual-specificity transcriptional repressor Kaiso, first identified in association with p120-catenin, is required for Xenopus gastrulation movements. In addition, depletion of xKaiso results in increased expression of the non-canonical xWnt11, which contributes to the xKaiso knockdown phenotype as it is significantly rescued by dominant-negative Wnt11. We further demonstrate that xWnt11 is a direct gene target of xKaiso and that p120-catenin association relieves xKaiso repression in vivo. Our results indicate that p120-catenin and Kaiso are essential components of a new developmental gene regulatory pathway that controls vertebrate morphogenesis.},\n\tnumber = {12},\n\tjournal = {Nature Cell Biology},\n\tauthor = {Kim, Si Wan and Park, Jae-Il and Spring, Christopher M. and Sater, Amy K. and Ji, Hong and Otchere, Abena A. and Daniel, Juliet M. and McCrea, Pierre D.},\n\tmonth = dec,\n\tyear = {2004},\n\tpmid = {15543138},\n\tpages = {1212--1220},\n}\n\n

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\n \n\n \n \n \n \n \n \n Regulation of the Rapsyn Promoter by Kaiso and δ-Catenin.\n \n \n \n \n\n\n \n Rodova, M.; Kelly, K. F.; VanSaun, M.; Daniel, J. M.; and Werle, M. J.\n\n\n \n\n\n\n Molecular and Cellular Biology, 24(16): 7188–7196. August 2004.\n \n\n\n\n
\n\n\n\n \n \n $\"Regulation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{rodova_regulation_2004,\n\ttitle = {Regulation of the {Rapsyn} {Promoter} by {Kaiso} and δ-{Catenin}},\n\tvolume = {24},\n\tissn = {0270-7306},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/15282317 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC479716 http://mcb.asm.org/cgi/doi/10.1128/MCB.24.16.7188-7196.2004},\n\tdoi = {10.1128/MCB.24.16.7188-7196.2004},\n\tabstract = {Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction. Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome. Kaiso is a POZ-zinc finger family transcription factor which recognizes the specific core consensus sequence CTGCNA (where N is any nucleotide). Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin. Here we show that delta-catenin, a brain-specific member of the p120 catenin subfamily, forms a complex with Kaiso. Antibodies against Kaiso and delta-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction. Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay. Minimal promoter assays demonstrated that the rapsyn promoter can be activated by Kaiso and delta-catenin; this activation is apparently muscle specific. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and delta-catenin. We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, delta-catenin, and myogenic transcription factors at the neuromuscular junction.},\n\tnumber = {16},\n\tjournal = {Molecular and Cellular Biology},\n\tauthor = {Rodova, M. and Kelly, K. F. and VanSaun, M. and Daniel, J. M. and Werle, M. J.},\n\tmonth = aug,\n\tyear = {2004},\n\tpmid = {15282317},\n\tpages = {7188--7196},\n}\n\n

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\n \n\n \n \n \n \n \n \n NLS-dependent nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression.\n \n \n \n \n\n\n \n Kelly, K. F.; Spring, C. M; Otchere, A. A; and Daniel, J. M\n\n\n \n\n\n\n Journal of Cell Science, 117(13): 2675–2686. June 2004.\n \n\n\n\n
\n\n\n\n \n \n $\"NLS-dependent$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{kelly_nls-dependent_2004,\n\ttitle = {{NLS}-dependent nuclear localization of p120ctn is necessary to relieve {Kaiso}-mediated transcriptional repression},\n\tvolume = {117},\n\tissn = {0021-9533},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/15138284 http://jcs.biologists.org/cgi/doi/10.1242/jcs.01101},\n\tdoi = {10.1242/jcs.01101},\n\tabstract = {The Armadillo catenin p120(ctn) regulates cadherin adhesive strength at the plasma membrane and interacts with the novel BTB/POZ transcriptional repressor Kaiso in the nucleus. The dual localization of p120(ctn) at cell-cell junctions and in the nucleus suggests that its nucleocytoplasmic trafficking is tightly regulated. Here we report on the identification of a specific and highly basic nuclear localization signal (NLS) in p120(ctn). The functionality of the NLS was validated by its ability to direct the nuclear localization of a heterologous beta-galactosidase-GFP fusion protein. Mutating two key positively charged lysines to neutral alanines in the NLS of full-length p120(ctn) inhibited both p120(ctn) nuclear localization as well as the characteristic p120(ctn)-induced branching phenotype that correlates with increased cell migration. However, while these findings and others suggested that nuclear localization of p120(ctn) was crucial for the p120(ctn)-induced branching phenotype, we found that forced nuclear localization of both wild-type and NLS-mutated p120(ctn) did not induce branching. Recently, we also found that one role of p120(ctn) was to regulate Kaiso-mediated transcriptional repression. However, it remained unclear whether p120(ctn) sequestered Kaiso in the cytosol or directly inhibited Kaiso transcriptional activity in the nucleus. Using minimal promoter assays, we show here that the regulatory effect of p120(ctn) on Kaiso transcriptional activity requires the nuclear translocation of p120(ctn). Therefore, an intact NLS in p120(ctn) is requisite for its first identified regulatory role of the transcriptional repressor Kaiso.},\n\tnumber = {13},\n\tjournal = {Journal of Cell Science},\n\tauthor = {Kelly, K. F. and Spring, Christopher M and Otchere, Abena A and Daniel, Juliet M},\n\tmonth = jun,\n\tyear = {2004},\n\tpmid = {15138284},\n\tpages = {2675--2686},\n}\n\n

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\n \n 2002\n \n \n (2)\n \n \n

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\n \n\n \n \n \n \n \n \n The p120ctn-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides.\n \n \n \n \n\n\n \n Daniel, J. M.; Spring, C. M; Crawford, H. C; Reynolds, A. B; and Baig, A.\n\n\n \n\n\n\n Nucleic Acids Research, 30(13): 2911–2919. July 2002.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 3 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{daniel_p120ctn-binding_2002,\n\ttitle = {The p120ctn-binding partner {Kaiso} is a bi-modal {DNA}-binding protein that recognizes both a sequence-specific consensus and methylated {CpG} dinucleotides},\n\tvolume = {30},\n\tissn = {13624962},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/12087177 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC117053 https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkf398},\n\tdoi = {10.1093/nar/gkf398},\n\tabstract = {The p120(ctn)-binding partner Kaiso is a new member of the POZ-zinc finger family of transcription factors implicated in development and cancer. To understand the role of Kaiso in gene regulation and p120(ctn)-mediated signaling and adhesion, we sought to identify Kaiso-specific DNA binding sequences and potential target genes. Here we demonstrate that Kaiso is a dual specificity DNA-binding protein that recognizes the specific consensus sequence TCCTGCNA as well as methyl-CpG dinucleotides. A minimal core sequence CTGCNA was identified as sufficient for Kaiso binding. Two copies of the Kaiso-binding site are present in the human and murine matrilysin promoters, implicating matrilysin as a candidate target gene for Kaiso. In electrophoretic mobility shift assays, matrilysin promoter-derived oligonucleotide probes formed a complex with GST-Kaiso fusion proteins possessing the zinc finger domain but not with fusion proteins lacking the zinc fingers. We further determined that only Kaiso zinc fingers 2 and 3 were necessary and sufficient for sequence-specific DNA binding. Interestingly, Kaiso also possesses a methyl-CpG-dependent DNA-binding activity distinct from its sequence-specific DNA binding. However, Kaiso has a higher affinity for the TCCTGCNA consensus than for the methyl-CpG sites. Furthermore, the DNA-binding ability of Kaiso with either recognition site was inhibited by p120(ctn). Kaiso thus appears to have two modes of DNA binding and transcriptional repression, both of which may be modulated by its interaction with the adhesion cofactor p120(ctn).},\n\tnumber = {13},\n\tjournal = {Nucleic Acids Research},\n\tauthor = {Daniel, J. M. and Spring, Christopher M and Crawford, Howard C and Reynolds, Albert B and Baig, Akeel},\n\tmonth = jul,\n\tyear = {2002},\n\tpmid = {12087177},\n\tpages = {2911--2919},\n}\n\n

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\n \n\n \n \n \n \n \n \n Isolation and Characterization of XKaiso, a Transcriptional Repressor That Associates with the Catenin Xp120ctn in Xenopus laevis.\n \n \n \n \n\n\n \n Kim, S. W.; Fang, X.; Ji, H.; Paulson, A. F.; Daniel, J. M.; Ciesiolka, M.; van Roy, F.; and McCrea, P. D.\n\n\n \n\n\n\n Journal of Biological Chemistry, 277(10): 8202–8208. March 2002.\n \n\n\n\n
\n\n\n\n \n \n $\"Isolation$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{kim_isolation_2002,\n\ttitle = {Isolation and {Characterization} of {XKaiso}, a {Transcriptional} {Repressor} {That} {Associates} with the {Catenin} {Xp120ctn} in {Xenopus} laevis},\n\tvolume = {277},\n\tissn = {0021-9258},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/11751886 http://www.jbc.org/lookup/doi/10.1074/jbc.M109508200},\n\tdoi = {10.1074/jbc.M109508200},\n\tabstract = {The Armadillo family of catenin proteins function in multiple capacities including cadherin-mediated cell-cell adhesion and nuclear signaling. The newest catenin, p120(ctn), differs from the classical catenins and binds to the membrane-proximal domain of cadherins. Recently, a novel transcription factor Kaiso was found to interact with p120(ctn), suggesting that p120(ctn) also possesses a nuclear function. We isolated the Xenopus homolog of Kaiso, XKaiso, from a Xenopus stage 17 cDNA library. XKaiso contains an amino-terminal BTB/POZ domain and three carboxyl-terminal zinc fingers. The XKaiso transcript was present maternally and expressed throughout early embryonic development. XKaiso's spatial expression was defined via in situ hybridization and was found localized to the brain, eye, ear, branchial arches, and spinal cord. Co-immunoprecipitation of Xenopus p120(ctn) and XKaiso demonstrated their mutual association, whereas related experiments employing differentially epitope-tagged XKaiso constructs suggest that XKaiso additionally self-associates. Finally, reporter assays employing a chimera of XKaiso fused to the GAL4 DNA binding domain indicate that XKaiso is a transcriptional repressor. These data suggest that XKaiso functions throughout development and that its repressor functions may be most apparent in the context of neural tissues. The significance of the XKaiso-p120(ctn) interaction has yet to be determined, but it may include transducing information from cadherin-mediated cell-cell contacts to transcriptional processes within the nucleus.},\n\tnumber = {10},\n\tjournal = {Journal of Biological Chemistry},\n\tauthor = {Kim, Si Wan and Fang, Xiang and Ji, Hong and Paulson, Alicia F. and Daniel, Juliet M. and Ciesiolka, Malgorzata and van Roy, Frans and McCrea, Pierre D.},\n\tmonth = mar,\n\tyear = {2002},\n\tpmid = {11751886},\n\tpages = {8202--8208},\n}\n\n

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\n \n 2001\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n Monoclonal Antibodies to Kaiso: A Novel Transcription Factor and p120ctn-Binding Protein.\n \n \n \n \n\n\n \n Daniel, J. M.; Ireton, R. C.; and Reynolds, A. B.\n\n\n \n\n\n\n Hybridoma, 20(3): 159–166. June 2001.\n \n\n\n\n
\n\n\n\n \n \n $\"Monoclonal$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{daniel_monoclonal_2001,\n\ttitle = {Monoclonal {Antibodies} to {Kaiso}: {A} {Novel} {Transcription} {Factor} and p120ctn-{Binding} {Protein}},\n\tvolume = {20},\n\tissn = {0272-457X},\n\turl = {http://www.liebertpub.com/doi/10.1089/027245701750293484},\n\tdoi = {10.1089/027245701750293484},\n\tabstract = {The POZ-zinc finger protein Kaiso belongs to a rapidly growing superfamily of BTB/POZ zinc finger transcription factors implicated in embryonic development and cancer. Kaiso interacts with the catenin p120ctn, but the significance of the interaction remains unknown. Although p120ctn is normally found in association with E-cadherin at cell-cell junctions, it can translocate to the nucleus under certain circumstances. Thus, the p120ctn-Kaiso interaction may regulate transcriptional events, as has been described previously for the classical catenin, β-catenin and the LEF1/TCF transcription factor. To facilitate further study of Kaiso and to determine the physiological relevance of its interaction with p120ctn, we have generated and characterized a panel of five Kaiso-specific monoclonal antibodies (MAbs) that function in immunoblotting, immunoprecipitation, and immunofluorescence analyses.},\n\tnumber = {3},\n\tjournal = {Hybridoma},\n\tauthor = {Daniel, Juliet M. and Ireton, Renee C. and Reynolds, Albert B.},\n\tmonth = jun,\n\tyear = {2001},\n\tpages = {159--166},\n}\n\n

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\n \n 2000\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n Selective Uncoupling of P120ctn from E-Cadherin Disrupts Strong Adhesion.\n \n \n \n \n\n\n \n Thoreson, M. A.; Anastasiadis, P. Z.; Daniel, J. M.; Ireton, R. C.; Wheelock, M. J.; Johnson, K. R.; Hummingbird, D. K.; and Reynolds, A. B.\n\n\n \n\n\n\n The Journal of Cell Biology, 148(1): 189–202. January 2000.\n \n\n\n\n
\n\n\n\n \n \n $\"Selective$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{thoreson_selective_2000,\n\ttitle = {Selective {Uncoupling} of {P120ctn} from {E}-{Cadherin} {Disrupts} {Strong} {Adhesion}},\n\tvolume = {148},\n\tissn = {0021-9525},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/10629228 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2156209 http://www.jcb.org/lookup/doi/10.1083/jcb.148.1.189},\n\tdoi = {10.1083/jcb.148.1.189},\n\tabstract = {p120ctn is a catenin whose direct binding to the juxtamembrane domain of classical cadherins suggests a role in regulating cell–cell adhesion. The juxtamembrane domain has been implicated in a variety of roles including cadherin clustering, cell motility, and neuronal outgrowth, raising the possibility that p120 mediates these activities. We have generated minimal mutations in this region that uncouple the E-cadherin–p120 interaction, but do not affect interactions with other catenins. By stable transfection into E-cadherin–deficient cell lines, we show that cadherins are both necessary and sufficient for recruitment of p120 to junctions. Detergent-free subcellular fractionation studies indicated that, in contrast to previous reports, the stoichiometry of the interaction is extremely high. Unlike α- and β-catenins, p120 was metabolically stable in cadherin-deficient cells, and was present at high levels in the cytoplasm. Analysis of cells expressing E-cadherin mutant constructs indicated that p120 is required for the E-cadherin–mediated transition from weak to strong adhesion. In aggregation assays, cells expressing p120-uncoupled E-cadherin formed only weak cell aggregates, which immediately dispersed into single cells upon pipetting. As an apparent consequence, the actin cytoskeleton failed to insert properly into peripheral E-cadherin plaques, resulting in the inability to form a continuous circumferential ring around cell colonies. Our data suggest that p120 directly or indirectly regulates the E-cadherin–mediated transition to tight cell–cell adhesion, possibly blocking subsequent events necessary for reorganization of the actin cytoskeleton and compaction.},\n\tnumber = {1},\n\tjournal = {The Journal of Cell Biology},\n\tauthor = {Thoreson, Molly A. and Anastasiadis, Panos Z. and Daniel, Juliet M. and Ireton, Reneé C. and Wheelock, Margaret J. and Johnson, Keith R. and Hummingbird, Diana K. and Reynolds, Albert B.},\n\tmonth = jan,\n\tyear = {2000},\n\tpmid = {10629228},\n\tpages = {189--202},\n}\n\n

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\n \n\n \n \n \n \n \n \n The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor.\n \n \n \n \n\n\n \n Daniel, J M; and Reynolds, A B\n\n\n \n\n\n\n Molecular and cellular biology, 19(5): 3614–23. May 1999.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 5 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{daniel_catenin_1999,\n\ttitle = {The catenin p120(ctn) interacts with {Kaiso}, a novel {BTB}/{POZ} domain zinc finger transcription factor.},\n\tvolume = {19},\n\tissn = {0270-7306},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/10207085 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC84161},\n\tdoi = {10.1128/mcb.19.5.3614},\n\tabstract = {p120(ctn) is an Armadillo repeat domain protein with structural similarity to the cell adhesion cofactors beta-catenin and plakoglobin. All three proteins interact directly with the cytoplasmic domain of the transmembrane cell adhesion molecule E-cadherin; beta-catenin and plakoglobin bind a carboxy-terminal region in a mutually exclusive manner, while p120 binds the juxtamembrane region. Unlike beta-catenin and plakoglobin, p120 does not interact with alpha-catenin, the tumor suppressor adenomatous polyposis coli (APC), or the transcription factor Lef-1, suggesting that it has unique binding partners and plays a distinct role in the cadherin-catenin complex. Using p120 as bait, we conducted a yeast two-hybrid screen and identified a novel transcription factor which we named Kaiso. Kaiso's deduced amino acid sequence revealed an amino-terminal BTB/POZ protein-protein interaction domain and three carboxy-terminal zinc fingers of the C2H2 DNA-binding type. Kaiso thus belongs to a rapidly growing family of POZ-ZF transcription factors that include the Drosophila developmental regulators Tramtrak and Bric à brac, and the human oncoproteins BCL-6 and PLZF, which are causally linked to non-Hodgkins' lymphoma and acute promyelocytic leukemia, respectively. Monoclonal antibodies to Kaiso were generated and used to immunolocalize the protein and confirm the specificity of the p120-Kaiso interaction in mammalian cells. Kaiso specifically coprecipitated with a variety of p120-specific monoclonal antibodies but not with antibodies to alpha- or beta-catenin, E-cadherin, or APC. Like other POZ-ZF proteins, Kaiso localized to the nucleus and was associated with specific nuclear dots. Yeast two-hybrid interaction assays mapped the binding domains to Arm repeats 1 to 7 of p120 and the carboxy-terminal 200 amino acids of Kaiso. In addition, Kaiso homodimerized via its POZ domain but it did not heterodimerize with BCL-6, which heterodimerizes with PLZF. The involvement of POZ-ZF proteins in development and cancer makes Kaiso an interesting candidate for a downstream effector of cadherin and/or p120 signaling.},\n\tnumber = {5},\n\tjournal = {Molecular and cellular biology},\n\tauthor = {Daniel, J M and Reynolds, A B},\n\tmonth = may,\n\tyear = {1999},\n\tpmid = {10207085},\n\tpages = {3614--23},\n}\n\n

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\n p120(ctn) is an Armadillo repeat domain protein with structural similarity to the cell adhesion cofactors beta-catenin and plakoglobin. All three proteins interact directly with the cytoplasmic domain of the transmembrane cell adhesion molecule E-cadherin; beta-catenin and plakoglobin bind a carboxy-terminal region in a mutually exclusive manner, while p120 binds the juxtamembrane region. Unlike beta-catenin and plakoglobin, p120 does not interact with alpha-catenin, the tumor suppressor adenomatous polyposis coli (APC), or the transcription factor Lef-1, suggesting that it has unique binding partners and plays a distinct role in the cadherin-catenin complex. Using p120 as bait, we conducted a yeast two-hybrid screen and identified a novel transcription factor which we named Kaiso. Kaiso's deduced amino acid sequence revealed an amino-terminal BTB/POZ protein-protein interaction domain and three carboxy-terminal zinc fingers of the C2H2 DNA-binding type. Kaiso thus belongs to a rapidly growing family of POZ-ZF transcription factors that include the Drosophila developmental regulators Tramtrak and Bric à brac, and the human oncoproteins BCL-6 and PLZF, which are causally linked to non-Hodgkins' lymphoma and acute promyelocytic leukemia, respectively. Monoclonal antibodies to Kaiso were generated and used to immunolocalize the protein and confirm the specificity of the p120-Kaiso interaction in mammalian cells. Kaiso specifically coprecipitated with a variety of p120-specific monoclonal antibodies but not with antibodies to alpha- or beta-catenin, E-cadherin, or APC. Like other POZ-ZF proteins, Kaiso localized to the nucleus and was associated with specific nuclear dots. Yeast two-hybrid interaction assays mapped the binding domains to Arm repeats 1 to 7 of p120 and the carboxy-terminal 200 amino acids of Kaiso. In addition, Kaiso homodimerized via its POZ domain but it did not heterodimerize with BCL-6, which heterodimerizes with PLZF. The involvement of POZ-ZF proteins in development and cancer makes Kaiso an interesting candidate for a downstream effector of cadherin and/or p120 signaling.\n

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\n \n 1997\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n Tyrosine phosphorylation and cadherin/catenin function.\n \n \n \n \n\n\n \n Daniel, J. M.; and Reynolds, A. B.\n\n\n \n\n\n\n BioEssays, 19(10): 883–891. October 1997.\n \n\n\n\n
\n\n\n\n \n \n $\"Tyrosine$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 1 download\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{daniel_tyrosine_1997,\n\ttitle = {Tyrosine phosphorylation and cadherin/catenin function},\n\tvolume = {19},\n\tissn = {0265-9247},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/9363682 http://doi.wiley.com/10.1002/bies.950191008},\n\tdoi = {10.1002/bies.950191008},\n\tabstract = {Cadherin-mediated cell-cell adhesion is perturbed in protein tyrosine kinase (PTK)-transformed cells. While cadherins themselves appear to be poor PTK substrates, their cytoplasmic binding partners, the Arm catenins, are excellent PTK substrates and therefore good candidates for mediating PTK-induced changes in cadherin behavior. These proteins, p120ctn, beta-catenin and plakoglobin, bind to the cytoplasmic region of classical cadherins and function to modulate adhesion and/or bridge cadherins to the actin cytoskeleton. In addition, as demonstrated recently for beta-catenin, these proteins also have crucial signaling roles that may or may not be related to their effects on cell-cell adhesion. Tyrosine phosphorylation of cadherin complexes is well documented and widely believed to modulate cell adhesiveness. The data to date, however, is largely correlative and the mechanism of action remains unresolved. In this review, we discuss the current literature and suggest models whereby tyrosine phosphorylation of Arm catenins contribute to regulation or perturbation of cadherin function.},\n\tnumber = {10},\n\tjournal = {BioEssays},\n\tauthor = {Daniel, Juliet M. and Reynolds, Albert B.},\n\tmonth = oct,\n\tyear = {1997},\n\tpmid = {9363682},\n\tpages = {883--891},\n}\n\n

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\n \n 1995\n \n \n (1)\n \n \n

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\n \n\n \n \n \n \n \n \n The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin.\n \n \n \n \n\n\n \n Daniel, J M; and Reynolds, A B\n\n\n \n\n\n\n Molecular and cellular biology, 15(9): 4819–24. September 1995.\n \n\n\n\n
\n\n\n\n \n \n $\"The$ Paper\n \n \n\n \n \n doi\n \n \n\n \n link\n \n \n\n bibtex\n \n\n \n \n \n abstract \n \n\n \n \n \n 2 downloads\n \n \n\n \n \n \n \n \n \n \n\n \n \n \n\n\n\n

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@article{daniel_tyrosine_1995,\n\ttitle = {The tyrosine kinase substrate p120cas binds directly to {E}-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin.},\n\tvolume = {15},\n\tissn = {0270-7306},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/7651399 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC230726},\n\tdoi = {10.1128/mcb.15.9.4819},\n\tabstract = {The tyrosine kinase substrate p120cas (CAS), which is structurally similar to the cell adhesion proteins beta-catenin and plakoglobin, was recently shown to associate with the E-cadherin-catenin cell adhesion complex. beta-catenin, plakoglobin, and CAS all have an Arm domain that consists of 10 to 13 repeats of a 42-amino-acid motif originally described in the Drosophila Armadillo protein. To determine if the association of CAS with the cadherin cell adhesion machinery is similar to that of beta-catenin and plakoglobin, we examined the CAS-cadherin-catenin interactions in a number of cell lines and in the yeast two-hybrid system. In the prostate carcinoma cell line PC3, CAS associated normally with cadherin complexes despite the specific absence of alpha-catenin in these cells. However, in the colon carcinoma cell line SW480, which has negligible E-cadherin expression, CAS did not associate with beta-catenin, plakoglobin, or alpha-catenin, suggesting that E-cadherin is the protein which bridges CAS to the rest of the complex. In addition, CAS did not associate with the adenomatous polyposis coli (APC) tumor suppressor protein in any of the cell lines analyzed. Interestingly, expression of the various CAS isoforms was quite heterogeneous in these tumor cell lines, and in the colon carcinoma cell line HCT116, which expresses normal levels of E-cadherin and the catenins, the CAS1 isoforms were completely absent. By using the yeast two-hybrid system, we confirmed the direct interaction between CAS and E-cadherin and determined that CAS Arm repeats 1 to 10 are necessary and sufficient for this interaction. Hence, like beta-catenin and plakoglobin, CAS interacts directly with E-cadherin in vivo; however, unlike beta-catenin and plakoglobin, CAS does not interact with APC or alpha-catenin.},\n\tnumber = {9},\n\tjournal = {Molecular and cellular biology},\n\tauthor = {Daniel, J M and Reynolds, A B},\n\tmonth = sep,\n\tyear = {1995},\n\tpmid = {7651399},\n\tpages = {4819--24},\n}\n\n

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