Article
BRAF oncogenic mutants evade autoinhibition through a common mechanism.
Science (New York, N.Y.) - 29 May 2025
Lavoie Hugo, Jin Ting, Lajoie Driss, Decossas Marion, Gendron Patrick, Wang Bing, Filandr Frantisek, Sahmi Malha, Hwa Jo Chang, Weber Sandra, Arseneault Geneviève, Tripathy Sasmita, Beaulieu Pierre, Schuetz Doris A, Schriemer David C, Marinier Anne, Rice William J, Maisonneuve Pierre, Therrien Marc
Abstract excerpt
Uncontrolled activation of the rat sarcoma (RAS)-extracellular signal-regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving monomeric autoinhibition and activation by dimerization, has been intensely scrutinized, but mechanisms enabling oncogenic mutants to evade regulation remain unclear. By using cryo-electron microscopy, we solved the...
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