PXD011124

PXD011124 is an original dataset announced via ProteomeXchange.

Title	Pervasive Roles of Ubiquitination in Orchestrating the Deubiquitinase Activity and Function of the BAP1/ASXL2 Tumor Suppressor Complex
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2018-09-28
AnnouncementXML	Submission_2018-09-28_08:25:46.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD011124
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Phospho; Deamidated; Oxidation; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-18 02:40:42	ID requested
⏵ 1	2018-09-28 08:25:47	announced

Dataset with its publication pending

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

Bachir El Affar
contact affiliation	Maisonneuve-Rosemont Hospital Research Center and Department of Medicine, University of Montréal, Montréal H3C 3J7, Québec, Canada
contact email	el.bachir.affar@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011124
     1. Label: PRIDE project
     2. Name: Pervasive Roles of Ubiquitination in Orchestrating the Deubiquitinase Activity and Function of the BAP1/ASXL2 Tumor Suppressor Complex