POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. Xu, Z., Kukekov, N. V., & Greene, L. A. The EMBO Journal, 22(2):252–261, January, 2003. ![POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex We report that the multidomain protein POSH (plenty of SH3s) acts as a scaffold for the JNK pathway of neuronal death. This pathway consists of a sequential cascade involving activated Rac1/Cdc42, mixed-lineage kinases (MLKs), MAP kinase kinases (MKKs) 4 and 7, c-Jun N-terminal kinases (JNKs) and c-Jun, and is required for neuronal death induced by various means including nerve growth factor (NGF) deprivation. In addition to binding GTP-Rac1 as described previously, we find that POSH binds MLKs both in vivo and in vitro, and complexes with MKKs 4 and 7 and with JNKs. POSH overexpression promotes apoptotic neuronal death and this is suppressed by dominant-negative forms of MLKs, MKK4/7 and c-Jun, and by an MLK inhibitor. Moreover, a POSH antisense oligonucleotide and a POSH small interfering RNA (siRNA) suppress c-Jun phosphorylation and neuronal apoptosis induced by NGF withdrawal. Thus, POSH appears to function as a scaffold in a multiprotein complex that links activated Rac1 and downstream elements of the JNK apoptotic cascade.
@article{xu_posh_2003,
title = {{POSH} acts as a scaffold for a multiprotein complex that mediates {JNK} activation in apoptosis},
volume = {22},
issn = {0261-4189},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC140096/},
doi = {10.1093/emboj/cdg021},
abstract = {We report that the multidomain protein POSH (plenty of SH3s) acts as a scaffold for the JNK pathway of neuronal death. This pathway consists of a sequential cascade involving activated Rac1/Cdc42, mixed-lineage kinases (MLKs), MAP kinase kinases (MKKs) 4 and 7, c-Jun N-terminal kinases (JNKs) and c-Jun, and is required for neuronal death induced by various means including nerve growth factor (NGF) deprivation. In addition to binding GTP-Rac1 as described previously, we find that POSH binds MLKs both in vivo and in vitro, and complexes with MKKs 4 and 7 and with JNKs. POSH overexpression promotes apoptotic neuronal death and this is suppressed by dominant-negative forms of MLKs, MKK4/7 and c-Jun, and by an MLK inhibitor. Moreover, a POSH antisense oligonucleotide and a POSH small interfering RNA (siRNA) suppress c-Jun phosphorylation and neuronal apoptosis induced by NGF withdrawal. Thus, POSH appears to function as a scaffold in a multiprotein complex that links activated Rac1 and downstream elements of the JNK apoptotic cascade.},
number = {2},
urldate = {2024-09-27},
journal = {The EMBO Journal},
author = {Xu, Zhiheng and Kukekov, Nickolay V. and Greene, Lloyd A.},
month = jan,
year = {2003},
pmid = {12514131},
pmcid = {PMC140096},
pages = {252--261},
}
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