PXD011124 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-09-18 02:40:42 | ID requested | |
⏵ 1 | 2018-09-28 08:25:47 | announced | |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD011124
- Label: PRIDE project
- Name: Pervasive Roles of Ubiquitination in Orchestrating the Deubiquitinase Activity and Function of the BAP1/ASXL2 Tumor Suppressor Complex