PXD044661
PXD044661 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | CRL4-DCAF15 control of cohesin dynamics sustains 1 cell proliferation |
| Description | The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency. Loss of DCAF15 results in suppression of AML through compromised replication fork integrity and consequent accumulation of DNA damage. Accordingly, DCAF15 loss sensitizes AML to replication stress-inducing therapeutics. Mechanistically, we discover that DCAF15 directly interacts with the SMC1A protein of the cohesin complex and destabilizes the cohesin regulatory factors PDS5A and CDCA5. Loss of PDS5A and CDCA5 removal precludes cohesin acetylation on chromatin, resulting in uncontrolled chromatin loop extrusion, defective DNA replication, and apoptosis. Collectively, our findings uncover an endogenous, cell autonomous function of DCAF15 in sustaining AML proliferation through post-translational control of cohesin dynamics. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-05-23 |
| AnnouncementXML | Submission_2024-05-23_06:34:05.402.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Hsin-Yao Tang |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl; Deamidated |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-08-19 08:58:32 | ID requested | |
| ⏵ 1 | 2024-05-23 06:34:05 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: DCAF15, cohesin |
Contact List
| Luca Busino | |
|---|---|
| contact affiliation | University of Pennsylvania, Perelman School of Medicine, Department of Cancer Biology, Philadelphia, PA |
| contact email | businol@upenn.edu |
| lab head | |
| Hsin-Yao Tang | |
| contact affiliation | The Wistar Institute |
| contact email | tangh@wistar.org |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v06/MSV000092697/ |
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