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BAP1 binds ASXL2. 89 / 90
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"ASXL2-BAP1 interactions have been shown to play a role in the suppression of solid tumorigenesis (e.g., human mesotheliomas and lung cancers), and ASXL2-BAP1 complexes, similar to ASXL1-BAP1 complexes, demonstrated to interact with BAP1-interacting proteins (e.g., YY1, FOXK1/2, OGT, and HCF1) [ xref ]."
36068610
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"Knock-in mice expressing BAP1 with a 3xFlag tag revealed that BAP1 interacts with HCF-1, OGT, and the polycomb group proteins ASXL1 and ASXL2 in vivo."
22878500
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"To validate interactions between the ASXL2 and BAP1 and to show that the ASXL2-AB box can regulate BAP1 deubiquitinase activity in cells, we performed co-IP-WB assays on purified proteins from transfected HEK 293 cells."
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19615732
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"Based on the molecular dynamics, kinetics, and stoichiometry of the intra- and inter-molecule domain-domain interactions between BAP1 and ASXL2 presented here, we draw the following conclusions."
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"First, all of the single- or co-expressed and purified recombinant BAP1 and ASXL2 domain/proteins or protein complexes from both bacteria and baculovirus are well-folded in structure and are functionally active."
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"Second, the interaction between BAP1 and ASXL2 is direct, specific, and stable to biochemical and biophysical manipulations."
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"With the exception of KDM1B, which appears to interact specifically with BAP1-ASXL2, the BAP1 interactome is essentially identical whether the complex forms around ASXL1 or ASXL2."
30664650
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33961781
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"ASXL2 binds an enzymatic protein, BAP1, to form a deubiquitinase (PR-DUB) complex that removes monoubiquitin from substrates such as histone 2A ."
37740028
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"Therefore, cancer-associated loss of BAP1 expression results in ASXL2 destabilization, and therefore the BAP1–ASXL2 interaction may play a role that remains to be defined in more detail in tumor suppression ( xref )."
32690542
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"Because most ASXL2 mutations are out-of-frame frameshift mutations in exons 11 and 12, at least in AML with t (18;21) [ xref ], the BAP1 binding region in ASXL2 is also unaffected, although it remains to be determined whether truncated ASXL2-BAP1 complexes exhibit enhanced DUB activity."
36068610
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"ASXL1 and ASXL2 compete for interaction with BAP1; BAP1-ASXL1 and BAP1-ASXL2 complexes have been shown to be present at similar levels in cells."
36068610
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"BAP1-ASXL2, but not ASXL1-BAP1 complexes, appears to mediate this tumor-suppressive function; overexpression of BAP1 or ASXL2, but not ASXL1, induces senescence, and deletion of the ASXM domain of ASXL2 impairs senescence (human fibroblasts IMR90 cell line) [ xref ]."
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"Consistent with this finding, our lab has shown that ASXL2 and BAP1 interact in vivo to regulate deubiquitination of uH2A [11] ."
25065743
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"However, while the role of ASXL2-BAP1 complexes and their associated proteins in normal and malignant hematopoiesis can be inferred from studies with solid malignancies, their precise function remains to be established."
36068610
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"Proteomic analysis of BAP1 interacting partners using this system revealed that BAP1 interacts with ASXL1 and ASXL2 in vivo as well as host cell factor 1 (HCF-1), O-GlcNAc transferase (OGT), and Forkhead box protein K1/2 (FOXK1/2)."
27527698
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"While we were not able to detect an association of BAP1 and ASXL2 in stem cell conditions, co-immunoprecipitation of BAP1 and ASXL1 revealed that BAP1:ASXL1 is the predominant complex in mTSCs ( xref and xref )."
34170818
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26416890
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"ASXL2 interacts with BAP1 in vivo and is required for efficient uH2A deubiquitination."
24040135
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"To determine whether this function is conserved in ASXL2, we examined the interaction between ASXL2 and BAP1, the mammalian homolog of Calypso, and the effect of Asxl2 deficiency on bulk uH2A level."
24040135
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26416890
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26416890
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26416890
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26186194
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"Does truncated ASXL1 impact ASXL2-BAP1 complex formation and function?"
36068610
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"Following the reviewers’ suggestions, we have conducted additional experiments to assess the endogenous interaction of BAP1-ASXL proteins by co-immunoprecipitating reciprocally BAP1-ASXL1 and BAP1-ASXL2 in stem cell conditions (new Figure 5C and Figure 5—figure supplement 1C)."
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"Does truncated ASXL2, like truncated ASXL1, have a higher affinity for BAP1 compared with WT ASXL2 that results in a hyperactive truncated ASXL2-BAP1 complex with enhanced histone H2A DUB activity?"
36068610
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"However, the role of the BAP1/ASXL2 complex in BAP1‐mutant UM is not well understood.The unique microenvironment of the liver may play a crucial role in the organotropism of BAP1‐mutant UM."
40300851
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"Because the interaction between BAP1 and ASXL2 is important for their stability and tumor suppression , we sought to investigate the potential role of ubiquitination in coordinating BAP1/ASXL2 stability and function."
30349006
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"Biochemical and structural data indicated that BAP1 interaction with the DEUBAD generates a Composite Ub Binding Interface (CUBI) that promotes DUB activity ."
30349006
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"Thus, we hypothesized that Ub binding by the BAP1/DEUBAD complex without actual catalysis is important for DEUBAD monoubiquitination and we sought to investigate this possibility."
30349006
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"As expected, based on previous studies , the unmodified DEUBAD/BAP1 complex retains a significant residual DUB activity in vitro (Fig. 7d)."
30349006
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"As the BAP1/ASXL2 complex regulate cell proliferation , we sought to determine the requirement of ASXL2 monoubiquitination in this process."
30349006
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"These results suggest that BAP1, ASXL2, and UBE2Es expression are correlated in mesothelioma tissues and are in further support of the functional interaction between UBE2Es and the BAP1/ASXL2 complex."
30349006
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"On the other hand, it is possible that the monoubiquitination of ASXL2 recruits other interacting partners to the BAP1/ASXL2 complex to enhance either substrate recognition or recruitment.We showed that nearly all the cellular pool of endogenous ASXL2 is monoubiquitinated."
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"Purification of DEUBAD/BAP1 complexes."
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"Proteomics analyses xref xref have observed interaction of BAP1 with ASXL2 DEU , but not yet with ASXL3 DEU ."
26739236
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"Moreover, we demonstrated that BAP1 interaction with ASXL2 regulates cell senescence and that ASXL2 cancer associated mutations disrupt BAP1 DUB activity."
26416890
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"ASXL2 interacts with BAP1 in vivo and is required for efficient uH2A deubiquitination."
24040135
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"To determine whether this function is conserved in ASXL2, we examined the interaction between ASXL2 and BAP1, the mammalian homolog of Calypso, and the effect of Asxl2 deficiency on bulk uH2A level."
24040135
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"Peng H. et al recently demonstrated how the interaction between BAP1 and ASXL2 is direct, and that this binding stimulates BAP1 hydrolase activity."
31401421
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"However, as expected, these BAP1 mutant proteins could still bind ASXL2 substrate, which was expected given that the missense mutations do not affect the carboxy-terminal ASXL1/2 binding domain of BAP1."
26719535
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"Cancer-derived mutation/deletion in the ASXL2 gene eliminates ASXL2 binding to BAP1, causing ASXL2 to lose its ability to stimulate BAP1 activity ( xref )."
| PMC
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"Despite evidence of clear physical interaction between ASXL1, ASXL2, and BAP1 as well as ASXL1 and the core PRC2 member SUZ12, interaction between ASXL2 and PRC2 members were not evident (XREF_SUPPLEMENTARY)."
28516957
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"ASXL2 binds an enzymatic protein, BAP1, to form a deubiquitinase (PR-DUB) complex that removes monoubiquitin from substrates such as histone 2A xref , xref ."
37740028
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27705803
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29284740
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27705803
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29284740
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"Peng H. et al recently demonstrated how the interaction between BAP1 and ASXL2 is direct, and that this binding stimulates BAP1 hydrolase activity."
31401421
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"Moreover, we demonstrated that BAP1 interaction with ASXL2 regulates cell senescence and that ASXL2 cancer-associated mutations disrupt BAP1 DUB activity."
26416890
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"ASXL2 interacts with the C-terminal domain of BAP1 and enhances PR-DUB activity."
38791157
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"Here, we show how these mutations affect BAP1 interactions with the Polycomb group-like protein ASXL2, using combinations of computational modeling technology, molecular biology, and in vitro reconstitution biochemistry."
29284740
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"We found that the BAP1-ASXL2 interaction is direct and high affinity, occurring through the ASXH domain of ASXL2, an obligate partner for BAP1 enzymatic activity."
29284740
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"Combined computational and biochemical approaches demonstrate that the BAP1-ASXL2 interaction is direct and high affinity and that many BAP1 mutations act allosterically to inhibit BAP1-ASXL2 binding."
29284740
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"In this study, we define molecular mechanisms whereby tumor-derived, discrete in-frame deletions and insertions outside of the BAP1 catalytic domain perturb BAP1-ASXL2 interactions leading to tumor-related loss of BAP1 catalytic activity."
29284740
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"To test this hypothesis and to explain how mutations/deletions/truncations occurring in either ULD or UCH domains inactivate BAP1 in cancer, we used computer predicted molecular modeling of these proteins as a guide and biochemically characterized the protein-protein and/or domain-domain interactions of BAP1 and ASXL2 in vivo and in vitro using highly purified recombinant proteins, in coordination with BAP1 ubiquitin enzymatic activity."
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"Direct interaction between BAP1 and ASXL2."
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"Association of BAP1 with ASXL2 was tested in vitro by binding of full-length BAP1 to ASXL2."
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"BAP1 was bound to ASXL2 (261–1435 aa) and ASXL2 (261–649 aa) ( xref )."
29284740
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"Since BAP1 associates with ASXL2 in vitro and in vivo , BAP1 ubiquitin hydrolase activity was tested using purified recombinant proteins produced from Bv."
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"When both proteins were mixed, ASXL2 greatly stimulated WT BAP1 activity, whereas a BAP1 mutant affecting the active cysteine (C91S) was enzymatically inactive ( xref ), indicating that ASXL2 not only binds to BAP1 but also stimulates its ubiquitin hydrolase activity."
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"These data indicate that ASXL2 stimulation of BAP1 ubiquitin hydrolase activity coordinates well with interactions between ASXL2 and BAP1 and that stimulation of BAP1 activity requires physical association of ASXL2 with BAP1."
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"For each BAP1/ASXL2 complex, 6 dishes of HEK293FT cells were transfected with 3 μg of pDEST-HA-BAP1 or pDEST-HA-BAP1 C91S and 30 μg of pDEST-Flag-ASXL2 or pDEST-Flag-ASXL2ΔMBH."
38849395
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"The BAP1/ASXL2 complexes were then eluted from the anti-FlagM2 beads using 200 μL of Flag peptide elution buffer (50 mM Tris pH 7.3, 150 mM NaCl, 1/500 anti-protease (sigma), 1 mM DTT, 1 mM PMSF, 0.2 mg/mL Flag peptide)."
38849395
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"The BAP1/ASXL2 complex regulates protein deubiquitination, particularly against histone H2A, thus affecting chromatin remodeling and gene expression (Daou et al. 2015; Peng et al. 2021; Sahtoe et al. 2016)."
40300851
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"However, the role of the BAP1/ASXL2 complex in UM is unknown."
40300851
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No evidence text available
28514442
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"While we were not able to detect an association of BAP1 and ASXL2 in stem cell conditions, co-immunoprecipitation of BAP1 and ASXL1 revealed that BAP1:ASXL1 is the predominant complex in mTSCs (Figure 5C and Figure 5—figure supplement 1C)."
34170818
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"Aliquots of the purifications were then flash frozen in dry ice and stored at −80 °C.The deubiquitination assays on native nucleosomes were done using the BAP1/ASXL2 complexes purified from HEK293FT cells."
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"However, BAP1 ULD mutants E631-A634 and R666-H669 significantly decreased UCH binding and almost completely abolished AB box binding ( xref ), consistent with in vitro binding of full-length BAP1 with ASXL2 (261–649 aa) shown in xref , xref ."
29284740
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"Herein, we have characterized protein-protein interactions of BAP1 and ASXL2 using computer modeling, biochemical approaches, and enzymatic activity analyses."
29284740
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"We demonstrate that interactions between BAP1 and ASXL2 are direct, specific, and stable to biochemical and biophysical manipulations as detected by isothermal titration calorimetry, GST association, and optical biosensor assays."
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"Tumor-derived in-frame mutations occurring outside of the BAP1-UCH domain disrupt the interaction between BAP1 and ASXL2, leading to loss of BAP1 catalytic activity."
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"We also perform experiments in human cells that validate the interactions between BAP1 and ASXL2, including that the ASXL-AB domain directly regulates BAP1 deubiquitinase activity."
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"Importantly, these new studies elucidate the molecular dynamics of these interactions, measure the kinetic and stoichiometric impact of mutations on protein binding and on the enzymatic activity of BAP1, and provide novel insights about the structural and dynamic parameters of the BAP1-ASXL2 interaction into single cell datasets that can inform future small-molecule approaches designed to reactivate latent wild-type UCH activity in BAP1 -mutant malignancies."
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"Using the structure of Drosophila Calypso UCH/ULD interaction with ASX (PDB 6HGC) converted into human BAP1 UCH/ULD and ASXL2 merged with our previous models of interaction with H2A and ubiquitin ( xref ), we can pinpoint the human contact maps of the ULD with ASXL2 with high confidence ( xref , xref )."
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