Matches in SemOpenAlex for { <https://semopenalex.org/work/W3172249841> ?p ?o ?g. }
- W3172249841 abstract "Although targeting BRAF mutants with RAF inhibitors has achieved promising outcomes in cancer therapy, drug resistance remains a remarkable challenge, and underlying molecular mechanisms are not fully understood. Here, we characterized a previously unknown group of oncogenic BRAF mutants with in-frame insertions (LLRins506 or VLRins506) of αC-β4 loop. Using structure modeling and molecular dynamics simulation, we found that these insertions formed a large hydrophobic network that stabilizes R-spine and thus triggers the catalytic activity of BRAF. Furthermore, these insertions disrupted BRAF dimer interface and impaired dimerization. Unlike BRAF(V600E), these BRAF mutants with low dimer affinity were strongly resistant to all RAF inhibitors in clinic or clinical trials, which arises from their stabilized R-spines. As predicted by molecular docking, the stabilized R-spines in other BRAF mutants also conferred drug resistance. Together, our data indicated that the stability of R-spine but not dimer affinity determines the RAF inhibitor resistance of oncogenic BRAF mutants." @default.
- W3172249841 created "2021-06-22" @default.
- W3172249841 creator A5002742346 @default.
- W3172249841 creator A5007586838 @default.
- W3172249841 creator A5016361904 @default.
- W3172249841 creator A5020068139 @default.
- W3172249841 creator A5029840134 @default.
- W3172249841 creator A5032739980 @default.
- W3172249841 creator A5035329250 @default.
- W3172249841 creator A5035657490 @default.
- W3172249841 creator A5046453739 @default.
- W3172249841 creator A5054532243 @default.
- W3172249841 creator A5058069305 @default.
- W3172249841 creator A5058396607 @default.
- W3172249841 creator A5059651266 @default.
- W3172249841 creator A5064708728 @default.
- W3172249841 date "2021-06-11" @default.
- W3172249841 modified "2023-09-29" @default.
- W3172249841 title "The stability of R-spine defines RAF inhibitor resistance: A comprehensive analysis of oncogenic BRAF mutants with in-frame insertion of αC-β4 loop" @default.
- W3172249841 cites W1031578623 @default.
- W3172249841 cites W1940641879 @default.
- W3172249841 cites W1949194567 @default.
- W3172249841 cites W1958258471 @default.
- W3172249841 cites W1970174659 @default.
- W3172249841 cites W1985309852 @default.
- W3172249841 cites W1985821753 @default.
- W3172249841 cites W1999613945 @default.
- W3172249841 cites W2004295816 @default.
- W3172249841 cites W2011780255 @default.
- W3172249841 cites W2011826559 @default.
- W3172249841 cites W2019661351 @default.
- W3172249841 cites W2033185023 @default.
- W3172249841 cites W2037779217 @default.
- W3172249841 cites W2043058822 @default.
- W3172249841 cites W2050456292 @default.
- W3172249841 cites W2051165598 @default.
- W3172249841 cites W2052420692 @default.
- W3172249841 cites W2054946171 @default.
- W3172249841 cites W2065283382 @default.
- W3172249841 cites W2076222956 @default.
- W3172249841 cites W2076883919 @default.
- W3172249841 cites W2079216025 @default.
- W3172249841 cites W2080534618 @default.
- W3172249841 cites W2080920431 @default.
- W3172249841 cites W2093815936 @default.
- W3172249841 cites W2099044540 @default.
- W3172249841 cites W2100794900 @default.
- W3172249841 cites W2102646127 @default.
- W3172249841 cites W2117475567 @default.
- W3172249841 cites W2124662474 @default.
- W3172249841 cites W2126329788 @default.
- W3172249841 cites W2128059000 @default.
- W3172249841 cites W2149662085 @default.
- W3172249841 cites W2155009402 @default.
- W3172249841 cites W2163188200 @default.
- W3172249841 cites W2166542272 @default.
- W3172249841 cites W2246110510 @default.
- W3172249841 cites W2298324804 @default.
- W3172249841 cites W2309935793 @default.
- W3172249841 cites W2334698485 @default.
- W3172249841 cites W2359678117 @default.
- W3172249841 cites W2424516564 @default.
- W3172249841 cites W2551781955 @default.
- W3172249841 cites W2727371002 @default.
- W3172249841 cites W2789665281 @default.
- W3172249841 cites W2883784555 @default.
- W3172249841 cites W2885615510 @default.
- W3172249841 cites W2899213690 @default.
- W3172249841 cites W2899372537 @default.
- W3172249841 cites W2905991105 @default.
- W3172249841 cites W2912868289 @default.
- W3172249841 cites W2952381571 @default.
- W3172249841 cites W2958387678 @default.
- W3172249841 cites W2978479061 @default.
- W3172249841 cites W3000124456 @default.
- W3172249841 cites W3015629149 @default.
- W3172249841 cites W3049642946 @default.
- W3172249841 doi "https://doi.org/10.1126/sciadv.abg0390" @default.
- W3172249841 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8189578" @default.
- W3172249841 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34108213" @default.
- W3172249841 hasPublicationYear "2021" @default.
- W3172249841 type Work @default.
- W3172249841 sameAs 3172249841 @default.
- W3172249841 citedByCount "12" @default.
- W3172249841 countsByYear W31722498412021 @default.
- W3172249841 countsByYear W31722498412022 @default.
- W3172249841 countsByYear W31722498412023 @default.
- W3172249841 crossrefType "journal-article" @default.
- W3172249841 hasAuthorship W3172249841A5002742346 @default.
- W3172249841 hasAuthorship W3172249841A5007586838 @default.
- W3172249841 hasAuthorship W3172249841A5016361904 @default.
- W3172249841 hasAuthorship W3172249841A5020068139 @default.
- W3172249841 hasAuthorship W3172249841A5029840134 @default.
- W3172249841 hasAuthorship W3172249841A5032739980 @default.
- W3172249841 hasAuthorship W3172249841A5035329250 @default.
- W3172249841 hasAuthorship W3172249841A5035657490 @default.
- W3172249841 hasAuthorship W3172249841A5046453739 @default.
- W3172249841 hasAuthorship W3172249841A5054532243 @default.
- W3172249841 hasAuthorship W3172249841A5058069305 @default.
- W3172249841 hasAuthorship W3172249841A5058396607 @default.