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PXD011124

PXD011124 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePervasive Roles of Ubiquitination in Orchestrating the Deubiquitinase Activity and Function of the BAP1/ASXL2 Tumor Suppressor Complex
DescriptionThe tumor suppressor and deubiquitinase (DUB) BAP1 regulates chromatin-associated processes and is frequently mutated in various malignancies. BAP1 and its drosophila orthologue Calypso assemble DUB complexes with ASXL-1, -2, -3 paralogues and ASX respectively, and these cofactors are required for stimulating their DUB activity. However how the DUB activity of BAP1 is regulated remains largely unknown. Here we show that BAP1 promotes monoubiquitination of ASXLs on the ASXM/DEUBAD domain. ASXL2 monoubiquitination promotes its stability or proteasomal degradation, stimulates BAP1 DUB activity and is required for mammalian cell proliferation. Monoubiquitination of ASXL2 is directly catalyzed by UBE2E family of ubiquitin conjugating enzymes and is regulated by deubiquitination. Monoubiquitination of ASX is regulated by Calypso and is required for drosophila development. We further revealed a switch mechanism that tightly regulate BAP1 function, as a monoubiquitination of BAP1 UCH domain is mutually exclusive with ASXL2 monoubiquitination, thus ensuring highly coordinated DUB-mediated signaling.
HostingRepositoryPRIDE
AnnounceDate2018-09-28
AnnouncementXMLSubmission_2018-09-28_08:25:46.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD011124
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterEric Bonneil
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListPhospho; Deamidated; Oxidation; Carbamidomethyl
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-09-18 02:40:42ID requested
12018-09-28 08:25:47announced
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project
curator keyword: Biomedical
submitter keyword: Histone H2AK119Ub
deubiquitination, Polycomb Group Proteins
BAP1
Calypso
ASXL
cell proliferation
Contact List
Bachir El Affar
contact affiliationMaisonneuve-Rosemont Hospital Research Center and Department of Medicine, University of Montréal, Montréal H3C 3J7, Québec, Canada
contact emailel.bachir.affar@umontreal.ca
lab head
Eric Bonneil
contact affiliationProteomic Platform
contact emaileric.bonneil@umontreal.ca
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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