⮝ Full datasets listing
PXD078309
PXD078309 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Repression of DNA Damage Response Sensitizes APL Cells to the Combined Genotoxicity of All-Trans Retinoic Acid and Arsenic Trioxide |
| Description | The synergistic combination of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO) has transformed acute promyelocytic leukemia (APL) from a terminal disease into a curable one. However, the molecular basis for the APL-specific synergy remains to be fully defined. In this work, we studied the mechanism that drives the unique efficacy of ATRA/ATO on APL cells. We found that the ATRA/ATO combination generates a high level of endogenous genotoxic stress, leading to exacerbated accumulation of DNA damage in APL cellular models and patient samples. Crucially, we found that ATRA-treatment triggers the ubiquitin-proteasome -mediated degradation of key DNA damage response proteins, including ATM and FANCD2. This APL-specific event is independent of PML-RARA turnover and creates a profound vulnerability to genotoxic stress, rendering APL cells more susceptible to the combined genotoxic stress from the ATRA-ATO combination. Our findings reveal that the synergized induction of genotoxic stress and the concurrent impairment of the DNA damage response mechanisms constitute a lethal "Double-Hit" that promotes APL-specific apoptosis. This study provides a novel paradigm for understanding therapeutic synergy and suggests that targeting DDR protein stability may extend the success of differentiation therapy to a broader range of leukemia. |
| HostingRepository | iProX |
| AnnounceDate | 2026-05-13 |
| AnnouncementXML | Submission_2026-05-13_20:09:32.838.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Landing Li |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Astral |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-05-13 20:09:06 | ID requested | |
| ⏵ 1 | 2026-05-13 20:09:33 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Acute promyelocytic leukemia, all-trans retinoic acid, differentiation therapy, DNA damage |
Contact List
| Lei Li | |
|---|---|
| contact affiliation | Zhejiang University |
| contact email | leili2020@zju.edu.cn |
| lab head | |
| Landing Li | |
| contact affiliation | Zhejiang University |
| contact email | landingli2021@outlook.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
