IndraLab

Statements

BAP1 binds ULD. 16 / 16
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"Mutations in BAP1-ULD , which occurs in several tumors, abolish the interaction with ASXL2 resulting in a missed stimulation on BAP1 activity."
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"His- or GST-tagged full-length BAP1, BAP1-UCH and BAP1-ULD domains were expressed in bacteria (Bac-) or baculovirus (Bv-), respectively ( xref )."
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"Biophysical and biochemical characterization of BAP1-UCH, BAP1-ULD, ASXL2-AB, and the UCH/ULD/AB complex."
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"Therefore, we initiated biochemical and biophysical analyses of the BAP1-UCH, BAP1-ULD, ASXL2-AB domains and protein complex."
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"The establishment of Ub-AMC assay and SPR for investigating protein-protein interactions would make it possible to validate small molecule hits in future screens for drug compounds that recover loss-of-function in cells with BAP1-ULD mutations/deletions ( xref )."
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"We next tested the affinity and kinetics of BAP1-ULD and ASXL2-AB using SPR."
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"Biochemical analyses of purified recombinant protein complexes from bacteria reveal a direct interaction between the BAP1-ULD domain and ASXL2-AB box."
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"Furthermore, our biochemical work demonstrated that the ASXL2-AB box binds to the BAP1-ULD domain, but not to BAP1-UCH."
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"Using computer molecular modeling of UCHL5 structures, we predicted that the BAP1-ULD domain folds back to the BAP1-UCH catalytic domain and that the ASXL2-AB box stabilizes the UCH catalytic loop via a unique BAP1 mechanism not seen in other UCH proteins, allowing for ubiquitin to fit into the active site ( xref , xref )."
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"Instead, the BAP1 ULD domain binds to the AB box, which leads to the formation of a stable ternary complex consisting of the BAP1-UCH, BAP1-ULD and ASXL2-AB domains ( xref – xref )."
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"The N-terminus of ASXL, which includes ASXH, binds the ULD domain of BAP1, allowing the UCH catalytic site to be brought in proximity to the target promoter."
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"We have demonstrated that ASXL, via its AB box, acts as a molecular scaffold to recruit the BAP1-ULD domain to transcription factors that bind to specific target genes; the BAP1-UCH catalytic domain then removes ubiquitin from histones on chromatin to regulate the expression of these transcriptional targets ( xref )."
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"Upon loss of binding of the ASXL-AB box to BAP1-ULD, BAP1 enzymatic activity is abolished, resulting in disturbances in BAP1-dependent chromatin state/gene expression that contribute to the pathogenesis of human malignancy and other diseases."
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"These data are consistent with our previous studies that used computer modeling technology to predict the molecular model of BAP1-ULD interacting with ASXL2-AB ( xref )."
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"From our previous computer modeling studies, BAP1-ULD is predicted to form a few long helices, while ASXL-AB box is predicted to form five helices ( xref )."
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"A stable ternary complex is formed, comprised of the BAP1-UCH, BAP1-ULD, and ASXL2-AB domains."
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