PXD059936

PXD059936 is an original dataset announced via ProteomeXchange.

Title	Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma
Description	Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981. Mechanistically, TAK-981 de-SUMOylates the cBAF/PBAF component, SMARCE1, stabilizing and restoring cBAF on chromatin, shifting away from SS18::SSX-driven transcription, resulting in DNA damage, cell death and tumor inhibition across both human and mouse SS tumor models. TAK-981 synergized with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX transcriptome, identifying a therapeutic vulnerability in SS.
HostingRepository	PRIDE
AnnounceDate	2025-08-07
AnnouncementXML	Submission_2025-08-07_13:15:48.381.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikhail Dozmorov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	sumoylated lysine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-18 04:37:37	ID requested
⏵ 1	2025-08-07 13:15:48	announced

Dataset with its publication pending

submitter keyword: synovial sarcoma

BAF complexes

SWI/SNF

SUMOylation

TAK-981

subasumstat

DNA damage

targeted therapy

Anthony C. Faber
contact affiliation	Virginia Commonwealth University
contact email	acfaber@vcu.edu
lab head
Mikhail Dozmorov
contact affiliation	Virginia Commonwealth University
contact email	mdozmorov@vcu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059936
     1. Label: PRIDE project
     2. Name: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma