PXD027441-1
PXD027441 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination. |
| Description | DNA double-strand breaks (DSBs) contribute to genome instability, a key feature of cancer. DSBs are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). We investigated the role of an isoform of the multifunctional cyclin-dependent kinase 9, CDK9-55, in DNA repair, by generating CDK9-55-knockout HeLa clones (through CRISPR-36 Cas9), which showed potential HR dysfunction. A phosphoproteomic screening in these clones treated with camptothecin revealed that CDC23 (cell division cycle 23), a component of the E3 ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), is a new substrate of CDK9-55, with S588 being its putative phosphorylation site. Mutated non-phosphorylatable CDC23(S588A) affected the repair pathway choice by impairing HR and favouring error prone NHEJ. Moreover, CDC23(S588A) promoted the ubiquitination of UFL1, a recently identified HR player. Overall, CDK9-55 could guide APC/C in choosing the correct DNA repair pathway, possibly by regulating UFL1 stability. This CDK9 role should be considered when designing CDK-inhibitor-based cancer therapies. |
| HostingRepository | MassIVE |
| AnnounceDate | 2022-08-24 |
| AnnouncementXML | Submission_2022-08-24_06:46:43.459.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 | Phospho; Oxidation |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-07-20 08:53:30 | ID requested | |
| ⏵ 1 | 2022-08-24 06:46:43 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Homologous Recombination, DNA repair pathway choice, CDK9, APC/C, Phosphoproteomics, LC-MS/MS |
Contact List
| Antonio Giordano | |
|---|---|
| contact affiliation | Sbarro Institute for Cancer Research and Molecular Medicine and Center of 16 Biotechnology, College of Science and Technology Temple University |
| contact email | giordano@temple.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/MSV000087856/ |
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