⮝ Full datasets listing
PXD071926
PXD071926 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Targeting p300 Driven PARP1 Acetylation to Reverse Acidic Microenvironment-Induced PARP Inhibitor Resistance |
| Description | PARP inhibitors (PARPi) resistance limits therapeutic efficacy. However, the contribution of the acidic tumor microenvironment (TME) to PARPi response has not been explored. Here, we demonstrate that the acidic TME drives a p300 dependent mechanism of PARPi resistance in epithelial ovarian cancer (EOC). A pathologically acidic pH enhances DNA damage repair, reduced PARPi mediated PARP1 trapping, and attenuates PARPi mediated anti tumor efficacy. An unbiased epigenetically focused CRISPR Cas9 screen revealed p300 as a druggable target for reversing acidic pH induced PARPi resistance. Mechanistically, we identified an ERK p300 PARP1 signaling axis activated under acidic pH, which alleviates PARPi induced PARP1 trapping and associated DNA damage by directly acetylating PARP1 on lysine 505 residue (PARP1 K505ac). Elevated PARP1 K505ac correlates with poorer overall survival and PARPi resistance. In patient derived and syngeneic EOC models, multiple p300 inhibitors synergize with PARPi to inhibit tumor growth. Together, our findings establish p300 as a promising therapeutic target for reversing acidosis-driven PARPi resistance. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-07-06 |
| AnnouncementXML | Submission_2026-07-06_06:44:34.781.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; Deamidated |
| Instrument | Q Exactive HF; Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-12-12 12:24:37 | ID requested | |
| ⏵ 1 | 2026-07-06 06:44:35 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: PARP1 Acetylation, PARP Inhibitor Resistance, DatasetType:Proteomics |
Contact List
| Rugang Zhang | |
|---|---|
| contact affiliation | MD Anderson |
| contact email | RZhang11@mdanderson.org |
| 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-ftp.ucsd.edu/v11/MSV000100203/ |
