PXD062535-1

PXD062535 is an original dataset announced via ProteomeXchange.

Title	CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing – phosphopeptides dataset
Description	Cyclin-dependent kinase 11 (CDK11) is essential for the regulation of pre-mRNA splicing via phosphorylation of the core spliceosome component SF3B1. This phosphorylation is a marker of the catalytically active spliceosomes thus it is important to identify the mechanisms that regulate CDK11 itself. Here, we report that a small subset of CDK11 is phosphorylated on the activation T-loop threonine 595 (Thr595) and is associated with the activated spliceosome on chromatin in gene bodies. Mutational analyses revealed that Thr595 is essential for the formation of the active CDK11 complex with cyclin L and SAP30BP. CDK11 transiently associates with CDK7, a transcriptional kinase that also promotes the activation of other CDKs. Inhibition of CDK7 initially decreases transcription, but longer durations of inhibition lead to production of unspliced pre-mRNAs. The onset of the CDK7-mediated splicing defect correlates with the sequential dephosphorylation of CDK11 Thr595 and SF3B1. SILAC-based phosphoproteomics upon brief CDK11 inhibition identified SF3B1, CDC5L and ESS2 as CDK11 substrates, which overlap with the previously identified CDK7 substrates in the spliceosome. In summary, our study suggests that CDK7 likely acts via CDK11 Thr595 phosphorylation to regulate pre-mRNA splicing in cells. The identification of additional CDK11 substrates points to its broader role in spliceosome regulation.
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_19:36:46.745.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD062535
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	David Potesil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-02 11:27:38	ID requested
⏵ 1	2025-12-28 19:36:47	announced

R, á, jeck, ý M, Gajdu, š, kov, á P, Man, í, k P, Hluch, ý M, Heged, ű, sov, á E, Kry, š, tofov, á K, Pot, ě, š, il D, Martinkov, á P, Slab, á Z, Khirsariya P, Š, ebesta M, Paruch K, Friedel CC, Zdr, á, hal Z, Blazek D, CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing. Nucleic Acids Res, 53(22):(2025) [pubmed]

10.6019/PXD062535;

10.1093/nar/gkaf1343;

submitter keyword: ots964, sf3b1,cdk7, cdk11, splicing, sy351

Zbynek Zdrahal
contact affiliation	Proteomics Core Facility and Research Group Proteomics, CEITEC-MU, Masaryk University, Brno, Czech Republic
contact email	zdrahal@sci.muni.cz
lab head
David Potesil
contact affiliation	Proteomics Core Facility and Research Group Proteomics CEITEC-MU Masaryk University Brno, Czech Republic
contact email	david.potesil@ceitec.muni.cz
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/2025/12/PXD062535

PRIDE project URI

• PRIDE
  1. PXD062535
     1. Label: PRIDE project
     2. Name: CDK7-CDK11 axis in spliceosome regulation and pre-mRNA splicing – phosphopeptides dataset