FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4317479912> ?p ?o ?g. }

• W4317479912 abstract "BAP1 is a powerful tumor suppressor gene characterized by haplo insufficiency. Individuals carrying germline BAP1 mutations often develop mesothelioma, an aggressive malignancy of the serosal layers covering the lungs, pericardium, and abdominal cavity. Intriguingly, mesotheliomas developing in carriers of germline BAP1 mutations are less aggressive, and these patients have significantly improved survival. We investigated the apparent paradox of a tumor suppressor gene that, when mutated, causes less aggressive mesotheliomas. We discovered that mesothelioma biopsies with biallelic BAP1 mutations showed loss of nuclear HIF-1α staining. We demonstrated that during hypoxia, BAP1 binds, deubiquitylates, and stabilizes HIF-1α, the master regulator of the hypoxia response and tumor cell invasion. Moreover, primary cells from individuals carrying germline BAP1 mutations and primary cells in which BAP1 was silenced using siRNA had reduced HIF-1α protein levels in hypoxia. Computational modeling and co-immunoprecipitation experiments revealed that mutations of BAP1 residues I675, F678, I679, and L691 -encompassing the C-terminal domain-nuclear localization signal- to A, abolished the interaction with HIF-1α. 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. Our data identify BAP1 as a key positive regulator of HIF-1α in hypoxia. We propose that the significant reduction of HIF-1α activity in mesothelioma cells carrying biallelic BAP1 mutations, accompanied by the significant reduction of HIF-1α activity in hypoxic tissues containing germline BAP1 mutations, contributes to the reduced aggressiveness and improved survival of mesotheliomas developing in carriers of germline BAP1 mutations." @default.
• W4317479912 created "2023-01-20" @default.
• W4317479912 creator A5000480138 @default.
• W4317479912 creator A5002313919 @default.
• W4317479912 creator A5008456013 @default.
• W4317479912 creator A5009720793 @default.
• W4317479912 creator A5011606705 @default.
• W4317479912 creator A5012419471 @default.
• W4317479912 creator A5030987631 @default.
• W4317479912 creator A5031330914 @default.
• W4317479912 creator A5036139303 @default.
• W4317479912 creator A5037522458 @default.
• W4317479912 creator A5038737702 @default.
• W4317479912 creator A5040501773 @default.
• W4317479912 creator A5043228034 @default.
• W4317479912 creator A5046225712 @default.
• W4317479912 creator A5050821617 @default.
• W4317479912 creator A5051401259 @default.
• W4317479912 creator A5052394856 @default.
• W4317479912 creator A5058278021 @default.
• W4317479912 creator A5059283487 @default.
• W4317479912 creator A5062184701 @default.
• W4317479912 creator A5068731692 @default.
• W4317479912 creator A5070952451 @default.
• W4317479912 creator A5083162338 @default.
• W4317479912 creator A5083444789 @default.
• W4317479912 creator A5085314376 @default.
• W4317479912 creator A5087506952 @default.
• W4317479912 creator A5089731664 @default.
• W4317479912 creator A5091299701 @default.
• W4317479912 date "2023-01-19" @default.
• W4317479912 modified "2023-10-14" @default.
• W4317479912 title "BAP1 is a novel regulator of HIF-1α" @default.
• W4317479912 cites W1532588118 @default.
• W4317479912 cites W1899503782 @default.
• W4317479912 cites W1929032511 @default.
• W4317479912 cites W1972002559 @default.
• W4317479912 cites W1973904343 @default.
• W4317479912 cites W1977376622 @default.
• W4317479912 cites W1981264193 @default.
• W4317479912 cites W1985458442 @default.
• W4317479912 cites W1985712533 @default.
• W4317479912 cites W1987134040 @default.
• W4317479912 cites W1989762654 @default.
• W4317479912 cites W1992898397 @default.
• W4317479912 cites W1999036451 @default.
• W4317479912 cites W2007541023 @default.
• W4317479912 cites W2008946188 @default.
• W4317479912 cites W2018393684 @default.
• W4317479912 cites W2018457031 @default.
• W4317479912 cites W2024052331 @default.
• W4317479912 cites W2034299708 @default.
• W4317479912 cites W2037312364 @default.
• W4317479912 cites W2057802075 @default.
• W4317479912 cites W2067441802 @default.
• W4317479912 cites W2070177764 @default.
• W4317479912 cites W2070195376 @default.
• W4317479912 cites W2075054245 @default.
• W4317479912 cites W2090817847 @default.
• W4317479912 cites W2094458603 @default.
• W4317479912 cites W2106996100 @default.
• W4317479912 cites W2108196925 @default.
• W4317479912 cites W2135037450 @default.
• W4317479912 cites W2143326470 @default.
• W4317479912 cites W2145290079 @default.
• W4317479912 cites W2146270900 @default.
• W4317479912 cites W2153057993 @default.
• W4317479912 cites W2218992355 @default.
• W4317479912 cites W2291531085 @default.
• W4317479912 cites W2329699996 @default.
• W4317479912 cites W2521282167 @default.
• W4317479912 cites W2556189512 @default.
• W4317479912 cites W2561826764 @default.
• W4317479912 cites W2572080171 @default.
• W4317479912 cites W2600632060 @default.
• W4317479912 cites W2611843839 @default.
• W4317479912 cites W2624817404 @default.
• W4317479912 cites W2734271067 @default.
• W4317479912 cites W2760275069 @default.
• W4317479912 cites W2797702016 @default.
• W4317479912 cites W2804822363 @default.
• W4317479912 cites W2806103948 @default.
• W4317479912 cites W2822628871 @default.
• W4317479912 cites W2892837443 @default.
• W4317479912 cites W2899300405 @default.
• W4317479912 cites W2903799300 @default.
• W4317479912 cites W2938922501 @default.
• W4317479912 cites W2949867299 @default.
• W4317479912 cites W2961780602 @default.
• W4317479912 cites W2962283999 @default.
• W4317479912 cites W2997191402 @default.
• W4317479912 cites W3014767592 @default.
• W4317479912 cites W3032355325 @default.
• W4317479912 cites W3042684909 @default.
• W4317479912 cites W3112235695 @default.
• W4317479912 cites W3124173816 @default.
• W4317479912 cites W3176944785 @default.
• W4317479912 cites W4224251450 @default.
• W4317479912 cites W4225274280 @default.
• W4317479912 doi "https://doi.org/10.1073/pnas.2217840120" @default.

• next