PXD003698-2

PXD003698 is an original dataset announced via ProteomeXchange.

Title	Identification of CDK8 and CDK19 substrates in human cells using cortistatin A and quantitative phosphoproteomics
Description	Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we report here the first large-scale identification of Mediator kinase substrates in human cells (HCT116). Among over 16,000 quantified sites, we identified 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data correlated with Mediator kinase targets, CA effects on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, which tracked about 7,000 proteins across six time points (0-24h), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation; contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest roles beyond transcription, including metabolism and DNA repair.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:09:43.433.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zach Poss
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-02-26 01:00:13	ID requested
1	2018-10-24 07:32:19	announced
⏵ 2	2024-10-22 04:09:51	announced	2024-10-22: Updated project metadata.

Poss ZC, Ebmeier CC, Odell AT, Tangpeerachaikul A, Lee T, Pelish HE, Shair MD, Dowell RD, Old WM, Taatjes DJ, Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics. Cell Rep, 15(2):436-50(2016) [pubmed]

10.1016/j.celrep.2016.03.030;

curator keyword: Biomedical

submitter keyword: Orbitrap Velos, proteomics, Mediator, quantitative, SILAC, Orbitrap LTQ,HCT116, colorectal carcinoma, CDK19, cortistatin A, phosphoproteomics, CDK8

Dylan J Taatjes
contact affiliation	Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado USA
contact email	dylan.taatjes@colorado.edu
lab head
Zach Poss
contact affiliation	University of Colorado
contact email	possz@colorado.edu
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/2018/10/PXD003698

PRIDE project URI

• PRIDE
  1. PXD003698
     1. Label: PRIDE project
     2. Name: Identification of CDK8 and CDK19 substrates in human cells using cortistatin A and quantitative phosphoproteomics