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A schematic diagram highlighting the role of G4 and G5 post-translational modifications in RAS activation. Monoubiquitylation of RAS at Lys117, as well as S-nitrosylation of RAS at Cys118, increases GDP dissociation, leading to an increased GTP/GDP exchange rate. In contrast, monoubiquitylation of RAS at Lys147 impedes GAP-mediated GTP hydrolysis, which populates the active RAS GTP-bound “ON” state.
