⮝ Full datasets listing
PXD066324-1
PXD066324 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | All-trans retinoic acid destabilizes ADAR1 protein through retinoylation-mediated USP7 dissociation and improves immunotherapy in pancreatic cancer |
| Description | ADAR1-p150 isoform, an interferon-stimulated double-stranded RNA-editing enzyme, contributes to immunotherapy resistance by suppressing interferon signaling. While genetic depletion of ADAR1 overcomes immunotherapy resistance in preclinical models, therapeutic targeting of ADAR1 has not been achieved to date in clinical setting. In this study, we found that the FDA-approved all-trans retinoic acid (ATRA) promoted ADAR1 protein degradation in different types of cancer. In addition, ATRA also induces the transcription of PD-L1 in cancer cells and the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment to unleash antitumor immunity, thereby impeding tumor growth in vivo. Mechanistically, we identified deubiquitinase USP7 as a key regulator for ADAR1 protein stability. ATRA disrupts the USP7-ADAR1 interaction, promoting ADAR1 degradation. Notably, the regulation of ADAR1 protein degradation by ATRA is independent of its canonical receptors. Instead, ATRA treatment leads to ADAR1 retinoylation, a post-translational modification by conjugation of retinoids, which results in the disruption of USP7-ADAR1 complex to promote ADAR1polyubiquitination. Importantly, clinical data shows a positive correlation between USP7 and ADAR1 protein expression in various cancers, supporting USP7's role in ADAR1 stabilization. Overall, this study sheds light on the control of ADAR1 protein turnover and proposes a mechanism-driven combination therapy using ATRA and PD-1/PD-L1 blockade to convert immunologically cold into hot tumors, holding potential for clinical translation. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-02-01 |
| AnnouncementXML | Submission_2026-02-01_04:33:00.976.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Yun Xiong |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | unknown modification |
| Instrument | Orbitrap Ascend |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-07-19 09:25:12 | ID requested | |
| ⏵ 1 | 2026-02-01 04:33:01 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: ADAR1, retinoylation, mass spectrometry, proteomics, DatasetType:Proteomics |
Contact List
| Yun Xiong | |
|---|---|
| contact affiliation | MD Anderson Cancer Center |
| contact email | yunxiong.omics@gmail.com |
| lab head | |
| Yun Xiong | |
| contact affiliation | MD Anderson Cancer Center |
| contact email | yunxiong.omics@gmail.com |
| 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/v10/MSV000098564/ |
