PXD052300 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
| 0 | 2024-05-16 05:23:35 | ID requested | |
| ⏵ 1 | 2026-04-26 17:40:48 | announced | |
Publication List
| 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; |
Keyword List
| submitter keyword: CDK9, MYC, Transcription, PROTACs, Ribosome Biogenesis |
Contact List
| 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 | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052300
- Label: PRIDE project
- Name: Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network