PXD078941

PXD078941 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-27 15:34:38	ID requested
⏵ 1	2026-08-04 05:16:30	announced

10.1084/JEM.20252333;

submitter keyword: APL,PML::RARA, SUMO, NCoR

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

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.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD078941

PRIDE project URI

• PRIDE
  1. PXD078941
     1. Label: PRIDE project
     2. Name: PML-driven sumoylation of PML::RARA-bound co-repressors drives immortalization of primary hematopoietic progenitors