PXD022333

PXD022333 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-04 01:38:24	ID requested
⏵ 1	2021-09-09 13:33:37	announced

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]

submitter keyword: CLK Kinases inhibitor, SRSF10, human colorectal cancer cells

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD022333

PRIDE project URI

• PRIDE
  1. PXD022333
     1. Label: PRIDE project
     2. Name: A novel class of CLK kinases inhibitors that target SRSF10 and promote p53mediated cytotoxicity on human colorectal cancer cells