PXD078941 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | PML-driven sumoylation of PML::RARA-bound co-repressors drives immortalization of primary hematopoietic progenitors |
| Description | While acute promyelocytic leukemia (APL) is always driven by fusions involving one of the three retinoic acid receptors, why PML and RARA are the preferred fusion partners has remained largely unsettled. Here we demonstrate that corepressor (NCoR) binding onto the RARA moiety of PML::RARA is required for hematopoietic progenitor immortalization. We establishthat PML-mediated tethering of the UBC9 SUMO conjugating enzyme onto PML::RARA enforces SUMO2 conjugation of multiple RARA partner proteins, notably the NCoR complex, boosting its repressive power. PML mutants that fail to recruit UBC9 yield PML::RARA fusions that neither promote NCoR sumoylation nor transformation. Conversely, direct UBC9/RARA fusion drivesboth efficient NCoR sumoylation and immortalization. Sumoylation inhibitors re-activate retinoic acid target genes in PML::RARA-, but not in RARA-, expressing progenitors and trigger APL differentiation. Thus, fusion of PML to RARA entails an unexpected gain of functionthat boosts RARA-mediated transcriptional repression through sumoylation of PML::RARA-bound proteins, explaining the recurrent implication of PML and RARA in APL pathogenesis. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-08-04 |
| AnnouncementXML | Submission_2026-08-04_05:16:29.783.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Viviane de Almeida Bastos |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | timsTOF HT |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-05-27 15:34:38 | ID requested | |
| ⏵ 1 | 2026-08-04 05:16:30 | announced | |
Publication List
Keyword List
| submitter keyword: APL,PML::RARA, SUMO, NCoR |
Contact List
| Hugues de Thé |
|---|
| contact affiliation | Collège de France, Oncologie Cellulaire et Moléculaire, PSL University, INSERM UMR 1050, CNRS UMR 7241 Paris, France |
| contact email | hugues.dethe@inserm.fr |
| lab head | |
| Viviane de Almeida Bastos |
|---|
| contact affiliation | Sorbonne University |
| contact email | viviane.de_almeida_bastos@sorbonne-universite.fr |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD078941
- Label: PRIDE project
- Name: PML-driven sumoylation of PML::RARA-bound co-repressors drives immortalization of primary hematopoietic progenitors
