PXD061476

PXD061476 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Confirmation of cdk8/19 inhibitor selectivity and activity in colorectal cancer
Description	The Mediator complex is an evolutionarily conserved regulator of gene expression, influencing chromatin structure and RNA polymerase II-mediated transcription. Its activity is modulated by a protein kinase module, which includes cyclin-dependent kinases 8 and 19, that phosphorylate RNA polymerase II and transcription factors to regulate gene expression. CDK8 exhibits both oncogenic and tumour-suppressive activities depending on the cellular context, while the contributions of CDK19 remain less well understood. Based on prior data with our CDK8/19 inhibitor - 3,4,5-trisubstituted pyridine compound CCT251545 - we selected the human colorectal cancer cell line COLO205 for profiling experiments. This model is highly dependent on mutant BRAF and oncogenic β-catenin-driven WNT signaling and exhibits high basal β-catenin-dependent TCF/LEF promoter activity, which is sensitive to CDK8/19 inhibition in vitro and in vivo.
HostingRepository	PRIDE
AnnounceDate	2025-07-28
AnnouncementXML	Submission_2025-07-27_16:06:37.960.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Clarke
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-04 15:14:27	ID requested
⏵ 1	2025-07-27 16:06:38	announced

Publication List

Ortiz-Ruiz MJ, Popoola O, Mitsopoulos K, Te-Poele R, Samant RS, Box G, Court W, Brandon AH, Gowan S, Mallinger A, Roe T, Swabey K, Valenti M, Al-Lazikani B, Blagg J, Esdar C, Schiemann K, Wienke D, Eccles SA, Workman P, Clarke PA, Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer. ACS Chem Biol, 20(7):1792-1804(2025) [pubmed]
10.1021/acschembio.5c00338;

Ortiz-Ruiz MJ, Popoola O, Mitsopoulos K, Te-Poele R, Samant RS, Box G, Court W, Brandon AH, Gowan S, Mallinger A, Roe T, Swabey K, Valenti M, Al-Lazikani B, Blagg J, Esdar C, Schiemann K, Wienke D, Eccles SA, Workman P, Clarke PA, Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer. ACS Chem Biol, 20(7):1792-1804(2025) [pubmed]

10.1021/acschembio.5c00338;

Keyword List

submitter keyword: inhibitor, CDK19,Phosphoproteome, CDK8, colorectal cancer

submitter keyword: inhibitor, CDK19,Phosphoproteome, CDK8, colorectal cancer

Contact List

Paul Clarke
contact affiliation	Centre for Cancer Drug Discovery Institute of Cancer Research London
contact email	Paul.clarke@icr.ac.uk
lab head
Paul Clarke
contact affiliation	Centre for Cancer Drug Discovery, Institute of Cancer Research
contact email	paul.clarke@icr.ac.uk
dataset submitter

Full Dataset Link List

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PRIDE project URI

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/2025/07/PXD061476

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Repository Record List

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