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BAP1 binds HIF1. 10 / 10
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"Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) experiments revealed that 1) HIF-1α and BAP1 bind to each other and co-precipitate (Fig. 2A), and 2) the nuclei of BAP1 cells contained significantly more PLA positive signals—evidence of BAP1 and HIF-1α interaction—than BAP1 cells (Fig. 2 B and C)."
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"The crystal structure of HIF-1α-HIF-1β complex (PDB ID: 4zpr) (49) shows that without BAP1, HIF-1α, and HIF-1β bind to DNA (49), thus BAP1 is not required for HIF-1α-HIF-1β complex formation."
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"Aligning the crystal structure of HIF-1α-HIF-1β complex (PDB ID: 4zpr) (49) to our structural model for the binding complex of BAP1-HIF-1α showed that both BAP1 and HIF-1β bind to the same residues of HIF-1α (1-73) on the DNA; however, in Fig. 3B, we demonstrate that BAP1, HIF-1α and the DNA form a complex without HIF-1β."
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"Therefore, our data indicate that BAP1 is not required for HIF-1α-HIF-1β complex formation to functionally bind to DNA, that HIF-1β is not required for BAP1-HIF-1α complex formation to functional binding to DNA, and that although DNA facilitates the binding of BAP1 and HIF-1α, it is not required to maintain the binding of both BAP1-HIF-1α and BAP1-HIF-1β."
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"In summary, our data suggest that BAP1 directly binds and stabilizes both HIF-1α and HIF-1β increasing their intra-nuclear availability for dimer formation, thus fine-tuning HIF activities required to support malignant cell growth."
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"So far, the pathogenic variants reported in ClinVar for both HIF-1α and HIF-1β are not located among the crucial residues of HIF-1α-r73 where HIF-1α can bind to BAP1, HIF-1β and DNA, or of HIF-1β (2-470) where HIF-1β can bind to BAP1, HIF-1α, and DNA."
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"We further investigated the specificity of the BAP1 interaction with HIF-1α in HEK-293 cells expressing Myc-BAP1 and HA-HIF-1α, using HA-Tag as bait."
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"To study the binding between BAP1 and HIF-1α, first, a rigid docking protocol was applied to model the binding complex of the CTD of BAP1 (the NLS domain is removed due to its flexibility) and HIF-1α by using the ClusPro server (43–45) (SI Appendix, Fig. S2B)."
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"Notably, BAP1 binding to HIF-1α-r73-DNA does not require HIF-1β for the interaction."
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"We tested the hypothesis that although DNA facilitates the binding between BAP1 and HIF-1α, this binding complex still holds in the absence of DNA."
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