PXD022515-2

PXD022515 is an original dataset announced via ProteomeXchange.

Title	Hexameric VCP/p97 reprograms transcription by organizing enhancers with the ASPSCR1-TFE3 fusion oncoprotein
Description	Aberrant transcription in alveolar soft part sarcoma (ASPS) is orchestrated by the fusion oncoprotein, ASPSCR1-TFE3, resulting from a gene fusion created by a t(X;17) chromosomal translocation. Proteomic analysis of co-immunoprecipitated ASPSCR1-TFE3 complexes revealed strong enrichment of VCP/p97, an AAA+ ATPase with known segregase function. VCP and ASPSCR1-TFE3 co-distributed across chromatin and were associated with active enhancers, indicated by flanking peaks of H3K27ac that assemble into higher order chromatin structures by HiChIP. Positive and negative genetic experiments with ASPSCR1-TFE3 and VCP demonstrated that they function co-dependently for cancer cell proliferation, colony formation, enhancer activation, chromatin conformation, and transcription. The VCP associating with ASPSCR1-TFE3 was found by native gel and electron microscopy to be assembled into homo-hexamers. Disruption of VCP hexamer assembly or enzymatic function inhibited the transcriptional impact of ASPSCR1-TFE3. Thus, a segregase was found to bind chromatin and assemble into 3-dimensional structures as a co-factor of transcriptional regulation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:15:40.383.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gian Luca Negri
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-13 03:14:10	ID requested
1	2023-11-23 05:37:32	announced
⏵ 2	2024-10-22 06:15:40	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: ASPS, IP-MS,TMT

Gregg Morin
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada
contact email	gmorin@bcgsc.ca
lab head
Gian Luca Negri
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gnegri@bcgsc.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022515
     1. Label: PRIDE project
     2. Name: Hexameric VCP/p97 reprograms transcription by organizing enhancers with the ASPSCR1-TFE3 fusion oncoprotein