PXD022333 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A novel class of CLK kinases inhibitors that target SRSF10 and promote p53mediated cytotoxicity on human colorectal cancer cells |
Description | The elevated expression of the splicing regulator SRSF10 in metastatic colorectal cancer (CRC) stimulates the production of the pro-tumorigenic Bclaf1-L splice variant. We discovered a group of small molecules with an aminothiazole carboxamide core (GPS167, GPS192 and others) that decrease production of Bclaf1-L. While additional alternative splicing events regulated by SRSF10 are affected by GPS167/192 in HCT116 cells (e.g., in MDM4, WTAP, SLK1 and CLK1), other events are shifted in a SRSF10-independent manner (e.g., in MDM2, NAB2 and TRA2A). GPS167/192 increased the interaction of SRSF10 with the CLK1 and CLK4 kinases, leading us to show that GPS167/192 are CLK kinase inhibitors preferentially impacting the activity of SRSF10. Notably, GPS167 impairs the growth of CRC cell lines and organoids, inhibits anchorage-independent colony formation, cell migration, and promotes cytoxicity that requires SRSF10 and p53. In contrast, GPS167 only minimally affects normal colonocytes and normal colorectal organoids. Thus, GPS167 reprograms the tumorigenic activity of SRSF10 in CRC cells to elicit p53-dependent apoptosis. |
HostingRepository | PRIDE |
AnnounceDate | 2021-09-09 |
AnnouncementXML | Submission_2021-09-09_13:33:37.056.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Lulzim Shkreta |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-11-04 01:38:24 | ID requested | |
⏵ 1 | 2021-09-09 13:33:37 | announced | |
Publication List
Sohail M, Shkreta L, Toutant J, Rabea S, Babeu JP, Huard C, Coulombe-Huntington J, Delannoy A, Placet M, Geha S, Gendron FP, Boudreau F, Tyers M, Grierson DS, Chabot B, A novel class of inhibitors that target SRSF10 and promote p53-mediated cytotoxicity on human colorectal cancer cells. NAR Cancer, 3(2):zcab019(2021) [pubmed] |
Keyword List
submitter keyword: CLK Kinases inhibitor, SRSF10, human colorectal cancer cells |
Contact List
Benoit Chabot |
contact affiliation | Department of Microbiology and Infectious Diseases.Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada |
contact email | Benoit.Chabot@USherbrooke.ca |
lab head | |
Lulzim Shkreta |
contact affiliation | Universite de Sherbrooke |
contact email | Lulzim.Shkreta@USherbrooke.ca |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022333
- Label: PRIDE project
- Name: A novel class of CLK kinases inhibitors that target SRSF10 and promote p53mediated cytotoxicity on human colorectal cancer cells