A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function. Fagan, V., Johansson, C., Gileadi, C., Monteiro, O., Dunford, J., E., Nibhani, R., Philpott, M., Malzahn, J., Wells, G., Faram, R., Cribbs, A., P., Halidi, N., Li, F., Chau, I., Greschik, H., Velupillai, S., Allali-Hassani, A., Bennett, J., Christott, T., Giroud, C., Lewis, A., M., Huber, K., V., M., Athanasou, N., Bountra, C., Jung, M., Schüle, R., Vedadi, M., Arrowsmith, C., Xiong, Y., Jin, J., Fedorov, O., Farnie, G., Brennan, P., E., & Oppermann, U. Journal of Medicinal Chemistry, 62(20):9008-9025, American Chemical Society, 10, 2019.
A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function [link]Website  abstract   bibtex   
Modifications of histone tails, including lysine/arginine methylation, provide the basis of a “chromatin or histone code”. Proteins that contain “reader” domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader domains and was identified as a putative oncogene and transcriptional coactivator. Here we report a SPIN1 chemical probe inhibitor with low nanomolar in vitro activity, exquisite selectivity on a panel of methyl reader and writer proteins, and with submicromolar cellular activity. X-ray crystallography showed that this Tudor domain chemical probe simultaneously engages Tudor domains 1 and 2 via a bidentate binding mode. Small molecule inhibition and siRNA knockdown of SPIN1, as well as chemoproteomic studies, identified genes which are transcriptionally regulated by SPIN1 in squamous cell carcinoma and suggest that SPIN1 may have a role in cancer related ...
@article{
 title = {A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function},
 type = {article},
 year = {2019},
 identifiers = {[object Object]},
 pages = {9008-9025},
 volume = {62},
 websites = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b00562},
 month = {10},
 publisher = {American Chemical Society},
 day = {24},
 id = {2b555f75-0963-3562-a9ba-557d46eac579},
 created = {2020-01-26T16:09:51.401Z},
 accessed = {2020-01-26},
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 profile_id = {64f7fb50-d000-335d-a02d-06c5f340a97a},
 last_modified = {2020-01-27T08:15:08.867Z},
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 abstract = {Modifications of histone tails, including lysine/arginine methylation, provide the basis of a “chromatin or histone code”. Proteins that contain “reader” domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader domains and was identified as a putative oncogene and transcriptional coactivator. Here we report a SPIN1 chemical probe inhibitor with low nanomolar in vitro activity, exquisite selectivity on a panel of methyl reader and writer proteins, and with submicromolar cellular activity. X-ray crystallography showed that this Tudor domain chemical probe simultaneously engages Tudor domains 1 and 2 via a bidentate binding mode. Small molecule inhibition and siRNA knockdown of SPIN1, as well as chemoproteomic studies, identified genes which are transcriptionally regulated by SPIN1 in squamous cell carcinoma and suggest that SPIN1 may have a role in cancer related ...},
 bibtype = {article},
 author = {Fagan, Vincent and Johansson, Catrine and Gileadi, Carina and Monteiro, Octovia and Dunford, James E. and Nibhani, Reshma and Philpott, Martin and Malzahn, Jessica and Wells, Graham and Faram, Ruth and Cribbs, Adam P. and Halidi, Nadia and Li, Fengling and Chau, Irene and Greschik, Holger and Velupillai, Srikannathasan and Allali-Hassani, Abdellah and Bennett, James and Christott, Thomas and Giroud, Charline and Lewis, Andrew M. and Huber, Kilian V. M. and Athanasou, Nick and Bountra, Chas and Jung, Manfred and Schüle, Roland and Vedadi, Masoud and Arrowsmith, Cheryl and Xiong, Yan and Jin, Jian and Fedorov, Oleg and Farnie, Gillian and Brennan, Paul E. and Oppermann, Udo},
 journal = {Journal of Medicinal Chemistry},
 number = {20}
}

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