PXD052300

PXD052300 is an original dataset announced via ProteomeXchange.

Title	Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network
Description	Cyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferation when their expression is deregulated. CDK9 modulation offers an approach for attenuating dysregulation in such transcriptional programs. As a result, numerous drug development campaigns to inhibit CDK9 kinase activity have been pursued. More recently, targeted degradation has emerged as an attractive approach. However, comprehensive evaluation of degradation versus inhibition is still critically needed to assess the biological contexts in which degradation might offer superior therapeutic benefits. We validated that CDK9 inhibition triggers a compensatory mechanism that dampens its effect on MYC expression and found that this feedback mechanism was absent when the kinase is degraded. Importantly, CDK9 degradation is more effective than its inhibition for disrupting MYC transcriptional regulatory circuitry likely through the abrogation of both enzymatic and scaffolding functions of CDK9.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-26_17:40:47.570.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD052300
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mohammed Toure
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-16 05:23:35	ID requested
⏵ 1	2026-04-26 17:40:48	announced

10.1016/j.chembiol.2025.03.001;

Toure MA, Motoyama K, Xiang Y, Urgiles J, Kabinger F, Koglin AS, Iyer RS, Gagnon K, Kumar A, Ojeda S, Harrison DA, Rees MG, Roth JA, Ott CJ, Schiavoni R, Whittaker CA, Levine SS, White FM, Calo E, Richters A, Koehler AN, Targeted degradation of CDK9 potently disrupts the MYC-regulated network. Cell Chem Biol, 32(4):542-555.e10(2025) [pubmed]

10.6019/PXD052300;

submitter keyword: CDK9, MYC, Transcription, PROTACs, Ribosome Biogenesis

Angela N. Koehler
contact affiliation	Massachusetts Institute of Technology
contact email	koehler@mit.edu
lab head
Mohammed Toure
contact affiliation	MIT
contact email	mtoure@mit.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/2026/04/PXD052300

PRIDE project URI

• PRIDE
  1. PXD052300
     1. Label: PRIDE project
     2. Name: Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network