PXD066230

PXD066230 is an original dataset announced via ProteomeXchange.

Title	A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation
Description	Controlled gene expression is achieved through the intricate regulation of Pol II progression through transcription-cycle checkpoints. While the contribution of CDK9 for Pol II pause-release is well established, the requirement for other CDKs has not been fully elucidated. Here we propose a new role for CDK11 in the Pol II pausing-to-elongation transition at a checkpoint that precedes and is independent from CDK9. Selective CDK11 inhibition or degradation results in acute ablation of RNA synthesis near the beginning of transcriptional units and genome-wide stalling of Pol II at TSS-proximal-regions. High-resolution chromatin-immunoprecipitation and precision-nuclear-run-on assays reveals spatial differences between CDK11- and CDK9-dependent Pol II pause sites, with CDK11 regulating Pol II upstream of the CDK9 checkpoint within the pausing zone. Cancer cells exhibit profound reliance on CDK11, with CDK11 inhibition reducing tumour burden in in vivo models of blood cancer, demonstrating the importance of CDK11-dependent Pol II regulation for aggressive haematological malignancies.
HostingRepository	PRIDE
AnnounceDate	2025-09-09
AnnouncementXML	Submission_2025-09-08_17:41:31.752.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Devlin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 16:57:37	ID requested
⏵ 1	2025-09-08 17:41:32	announced

10.1016/j.molcel.2025.08.001;

Devlin JR, Martin B, Bartonicek N, Ting K, Fan Z, Todorovski I, Bjelosevic F, Verschoor S, Ciccone A, Trapani JA, Horvath A, Tinsley E, Fraser P, Newbold A, Sandow JJ, Muscat A, Simpson KJ, Geyer M, Vervoort SJ, Johnstone RW, A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation. Mol Cell, 85(17):3256-3274.e14(2025) [pubmed]

submitter keyword: CDK11,transcription, pause-release, leukaemia

Ricky W. Johnstone
contact affiliation	Executive Director Cancer Research Group Leader, Gene Regulation Lab Peter MacCallum Cancer Centre, Parkville VIC 3052, Australia
contact email	ricky.johnstone@petermac.org
lab head
Jennifer Devlin
contact affiliation	Peter MacCallum Cancer Centre
contact email	jennifer.devlin@petermac.org
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/2025/09/PXD066230

PRIDE project URI

• PRIDE
  1. PXD066230
     1. Label: PRIDE project
     2. Name: A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation