IndraLab

Statements

BAP1 is ubiquitinated. 33 / 33
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"BAP1 ubiquitination affinity is increased by DEUBAD domains (DEUBiquitinase ADaptor) of ASXL1/2/3 ."
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"Moreover, we found that VCP inhibitors inhibited CCA cell growth and promoted cell apoptosis by blocking BAP1 ubiquitination degradation."
40122668
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"Ubiquitylation of BAP1 near its nuclear localization sequence negatively regulates its activity by excluding BAP1 from the nucleus, where most of its targets reside [84] ."
26073511
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"Investigated several E2s and DUBs demonstrated that UBE2O is specifically directed against ubiquitination of BAP1."
37533513
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"The conserved region 1(CR1), conserved region 2 (CR2), and UBC domains of UBE2O are necessary for the ubiquitination of BAP1 because deletion of anyone of them abolishes the ability of UBE2O to bring ubiquitination of BAP1."
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"Consistently, depletion of VCP markedly elevated the BAP1 ubiquitination level (Figure  xref )."
40122668
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"Under normal growth conditions BAP1 is predominantly nuclear, whereas UBE2O is mainly cytoplasmic, suggesting that BAP1 ubiquitination is highly regulated."
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"Further, deletion of N or C terminal regions of UBE2O has been found to entirely disrupt ubiquitylation of BAP1 [ xref ]."
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"UBE2O could be imported into the nucleus to ubiquitinate BAP1 and promote its ubiquitin-mediated nuclear export as observed for other proteins ( Groulx and Lee, 2002; Li et al., 2003 )."
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"Controlling UBE2O import itself would provide another level of regulation for the fine-tuning of BAP1 ubiquitination."
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"In addition, UBE2O can function in BMP7-induced adipogenesis via monoubiquitination of SMAD6 and also in chromatin remodeling by ubiquitinating the tumor-suppressive DUB BAP1 ( xref )."
37533513
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"The conserved region 1(CR1), conserved region 2 (CR2), and UBC domains of UBE2O are necessary for the ubiquitination of BAP1 because deletion of anyone of them abolishes the ability of UBE2O to bring ubiquitination of BAP1."
37533513
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"Our study demonstrated that VCP functions as the key upstream regulator mediating BAP1's ubiquitination degradation, and targeting VCP to indirectly regulate the protein level of BAP1, rather than targeting the mutant BAP1, is more suitable for most CCA patients."
40122668
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"On the other hand, since ubiquitination of BAP1 is counteracted by autodeubiquitination, one can predict that a yet-to-be-identified signal is needed to inactivate BAP1 catalytic activity."
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"Under normal cell growth conditions, UBE2O-mediated ubiquitination of BAP1 might not necessarily lead to a net accumulation of BAP1 in the cytoplasm, since this could be a protracted process that is c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"An siRNA screen for DUBs that affect levels of ubiquitylated γ-tubulin identified BAP1 and UCHL1 as candidates [ xref ]."
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"We therefore turned to another established property of BAP1, namely modification of H2A. Indeed, immunoblot of H2AK119ub1 reveals increased bulk histone ubiquitination in Bap1 ∆ LysM macrophages and differentiating osteoclasts (Fig.  xref )."
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"Then ubiquitinated BAP1 was also evaluated by anti-BAP1 IP followed by anti-Myc western analysis (Fig. xref c,d)."
26081045
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"It offers a novel therapeutic target for CCA treatment: targeting VCP With its inhibitors significantly inhibited CCA growth by blocking BAP1 ubiquitination degradation in vitro/in vivo."
40122668
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"Therefore, BAP1 may be functionally inactivated in these cases with alterations of UBE2O or other genes involved in BAP1 ubiquitination, specifically in nuclear BAP1-negative but cytosolic positive tumors."
26081045
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"The lysine residues near the nuclear localization sequence (NLS) of BAP1 can be ubiquitinated, which leads to the accumulation of ubiquitinated BAP1 in the cytosol."
34177595
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"This is also due to the ubiquitination of BAP1 near the NLS by UBE2O. Studies have shown that the auto-deubiquitination of BAP1 can counteract this process through intramolecular interactions, thereby ensuring its function in tumour suppression ( xref ; xref )."
34177595
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"Thus, UBE2O-mediated ubiquitination of BAP1 might constitute a quality control mechanism that prevents the nuclear import of an improperly folded DUB."
35764170
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"To identify E3 ligases responsible for the ubiquitination of BAP1, we initially considered UBE2O which was more abundant in the C91S versus the wild-type BAP1 complex ( Figure 1 A)."
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"To control for the specificity of UBE2O-mediated BAP1 ubiquitination, we evaluated other E2s, and none was able to ubiquitinate BAP1 ( Figures S1 H and S1I)."
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"This may suggest that the binding between BAP1 and HSF1 could inhibit the ubiquitination of BAP1 mediated by UBE2O [ xref ], or there may be other unexplored mechanisms at play."
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"Deletion of either N-terminal (ΔCR1-CR2) or C-terminal (ΔC) regions of UBE2O completely disrupted BAP1 ubiquitination ( Figures 1 D and 1E)."
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"Hence, the integrity of multiple domains of UBE2O is required for ubiquitination of BAP1."
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"To determine the mechanism of UBE2O action on BAP1, we established an in vitro assay for BAP1 ubiquitination using wild-type and C91S complexes immobilized on the beads ( Figure S2 A)."
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"Notably, we did not detect ubiquitination of wild-type BAP1 as opposed to C91S, and this ubiquitination was completely abolished by the UBE2O inhibitor PAO ( Figures 2 A and S2 B)."
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"However, BAP1 can be ubiquitylated by ubiquitin-conjugating enzyme E2 O (UBE2O) at its NLS to promote nuclear export xref ."
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"Thus, multiple determinants of this composite and highly conserved NLS are required for UBE2O-mediated ubiquitination of BAP1 ( Figure S3 H)."
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"Therefore, we evaluated whether the ubiquitination of BAP1 affects its subcellular localization."
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