The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS

Paving the way for KRAS inhibitors KRAS is a key oncogene in multiple cancer types, but existing inhibitors target only a mutant form of KRAS containing the G12C mutation, and their function presents a mechanistic conundrum. It is known that KRAS G12C inhibitors bind to the oncoprotein in its inactive form; however, KRAS mutations such as G12C interfere with the action of proteins that normally help it hydrolyze GTP to achieve the inactive state. Li et al . have now identified a protein that enhances GTP hydrolysis by mutant KRAS, helping to explain the clinical activity of current drugs targeting this oncoprotein (see the Perspective by Cox and Der). —YN