IndraLab

Statements


4 | 1 15

sparser
"We demonstrated that during hypoxia, BAP1 binds, deubiquitylates, and stabilizes HIF-1α, the master regulator of the hypoxia response and tumor cell invasion."

reach
"HIF1alpha-dependent metabolism:. Bioinformatics interrogation of The Cancer Genome Atlas (TCGA) data have associated BAP1 alterations with changes in hypoxia-inducible factor-1 alpha (HIFα) expression (25,76,77)."

sparser
"BAP1 is a key positive regulator of HIF-1α in hypoxia and binds to the N-terminal region of HIF-1α, where HIF-1α recognizes DNA and dimerizes with HIF-1β to form the heterodimeric transactivating complex HIF."

sparser
"We found that BAP1 binds to the N-terminal region of HIF-1α, where HIF-1α binds DNA and dimerizes with HIF-1β forming the heterodimeric transactivating complex HIF."

sparser
"BAP1 Interacts with HIF-1α."

sparser
"Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) experiments revealed that 1) HIF-1α and BAP1 bind to each other and co-precipitate ( xref ), and 2) the nuclei of BAP1 WT cells contained significantly more PLA positive signals—evidence of BAP1 and HIF-1α interaction—than BAP1 +/− cells ( xref )."

sparser
"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."

sparser
"We established a computational model of the binding complex of BAP1 and HIF-1α."

sparser
"The NLS domain of BAP1 binds to HIF-1α-r73 and the thermodynamic stability of the binding complex increases through electrostatic interactions with DNA."

sparser
"CoIP experiments in cells co-transfected with full-length Myc-tagged BAP1 (Myc- BAP1 ) and HA-tagged full-length HIF-1α, or HIF-1α fragments covering residues 74 to 826 [HIF-1α(74-826)], 2-400 [HIF-1α(2-400)], 401-826 [HIF-1α(401-826)] ( xref ), confirmed that BAP1 binds to the N terminus region of HIF-1α [HIF-1α(2-400)] ( xref )."

sparser
"As predicted by our computational model, residues 1 to 73 of HIF-1α are essential for the interaction because HIF-1α(74-826) did not bind BAP1 ( xref )."

sparser
"All four residues forming the hydrophobic core of BAP1 must be mutated to completely abolish the binding of HIF-1α, while in the presence of single point mutations BAP1 interaction with HIF-1α is decreased but not entirely abolished ( xref )."

sparser
"A decrease in nuclear HIF-1α signal was observed in mesothelioma cases with germline BAP1 mutations, particularly those with biallelic mutations, which revealed BAP1’s interaction with HIF-1α ( xref )."

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sparser
"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."

sparser
"As recently investigated, BAP1 binds to HIF-1α [ xref ], thus regulating its activity."

sparser
"In addition, we observed that hypoxic conditions increase exogenous BAP1 expression, raising the possibility of future studies to investigate HIF1α-BAP1 cross-talk, and its role in metabolic alterations."