ArticleNature communications2018
Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 78 citations in OpenAlex.
- Unique gluing effect of ASXL1 K351 monoubiquitination stimulates the PR-DUB activity.Nature chemical biology · 2026Article
- Substrate biasing in UCHL5 proteoforms.bioRxiv : the preprint server for biology · 2026Article
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Unleashed condensation by recurrent mutations of an epigenetic regulator promotes cancer.bioRxiv : the preprint server for biology · 2026Article
- Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4.Nature communications · 2026Article
- Unconventional structure and function of PHD domains from additional sex combs-like proteins.The FEBS journal · 2025Article
- Integrated multi-omics analysis identifies key biomarkers associated with post-translational modifications and RNA methylation in clear cell renal cell carcinoma.Discover oncology · 2025Article
- BAP1 Loss Affords Lipotoxicity Resistance in Uveal Melanoma.Pigment cell & melanoma research · 2025Article
- LN-439A, a novel BAP1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5.Acta pharmacologica Sinica · 2025Article
- A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Case Report: A familial hematological pedigree reveals VHL germline mutation as a principal predisposition factor with additional mutations modulating phenotypic heterogeneity.Frontiers in oncology · 2025Article
- Integrative analysis of ASXL family genes reveals ASXL2 as an immunoregulatory molecule in head and neck squamous cell carcinoma.Scientific reports · 2024Article
- BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers.Nature communications · 2024Article
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1.Frontiers in immunology · 2024Article
- PR-DUB safeguards Polycomb repression through H2AK119ub1 restriction.Cell proliferation · 2023Article
- BAP1 promotes osteoclast function by metabolic reprogramming.Nature communications · 2023Article
- BAP1-related signature predicts benefits from immunotherapy over VEGFR/mTOR inhibitors in ccRCC: a retrospective analysis of JAVELIN Renal 101 and checkmate-009/010/025 trials.Cancer immunology, immunotherapy : CII · 2023Article
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
The tumor suppressor and deubiquitinase (DUB) BAP1 and its Drosophila ortholog Calypso assemble DUB complexes with the transcription regulators Additional sex combs-like (ASXL1, ASXL2, ASXL3) and Asx respectively. ASXLs and Asx use their DEUBiquitinase ADaptor (DEUBAD) domain to stimulate BAP1/Calypso DUB activity. Here we report that monoubiquitination of the DEUBAD is a general feature of ASXLs and Asx. BAP1 promotes DEUBAD monoubiquitination resulting in an increased stability of ASXL2, which in turn stimulates BAP1 DUB activity. ASXL2 monoubiquitination is directly catalyzed by UBE2E family of Ubiquitin-conjugating enzymes and regulates mammalian cell proliferation. Remarkably, Calypso also regulates Asx monoubiquitination and transgenic flies expressing monoubiquitination-defective Asx mutant exhibit developmental defects. Finally, the protein levels of ASXL2, BAP1 and UBE2E enzymes are highly correlated in mesothelioma tumors suggesting the importance of this signaling axis for tumor suppression. We propose that monoubiquitination orchestrates a molecular symbiosis relationship between ASXLs and BAP1.
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