PXD028470
PXD028470 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A pan-cancer study to identify and characterize synthetic lethal drugs in BAP1-deficient cancers |
| Description | BRCA-1 Associated Protein (BAP1) is a deubiquitinating enzyme that acts as a tumour suppressor. Inactivating mutations in the BAP1 gene have been identified in many cancers including cholangiocarcinoma, hepatocellular carcinoma, mesothelioma, uveal melanoma and renal cell carcinoma. Current standard therapeutic approaches for BAP1-deficient tumours are not particularly promising, contributing to poor overall survival and disease-free survival rates. Here, we found BAP1 to mediate the turnover of the key proteins in the DNA nucleotide excision repair (NER) pathway, and therefore promotes DNA repair. Importantly, we demonstrate that the loss of functional BAP1 sensitise tumour cells to LSD1 inhibitor, SP2509, in vitro and in vivo, through further impairment of NER efficiency. When used in combination with PARP1 inhibitor, Olaparib, we show that a synergistic drug combination response is achieved. Overall, our study identifies a drug combination approach that has the potential to be exploited clinically to target BAP1 deficient tumours. |
| HostingRepository | jPOST |
| AnnounceDate | 2022-09-15 |
| AnnouncementXML | Submission_2022-09-18_03:42:31.986.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Radoslaw Sobota |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
| ModificationList | S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; alpha-amino acetylated residue; deamidated L-glutamine; deamidated L-asparagine; ubiquitinylated lysine |
| Instrument | instrument |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-09-14 20:25:37 | ID requested | |
| 1 | 2022-09-14 08:00:05 | announced | |
| ⏵ 2 | 2022-09-18 03:42:32 | announced | 2022-09-18: Updated FTP location. |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: cholangiocarcinoma, deubiquitination, BAP1, mass spectrometry |
Contact List
| Radoslaw Mikolaj Sobota | |
|---|---|
| lab head | |
| Radoslaw Sobota | |
| contact affiliation | IMCB A-STAR Singapore |
| dataset submitter | |
Full Dataset Link List
| jPOST 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://ftp.jpostdb.org/JPST001219/ |
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