Open AccessThe G protein signaling regulator RGS3 enhances the GTPase activity of KRAS
Author(s) -
Chuanchuan Li,
Alberto Vides,
Dong-Sung Kim,
Jenny Y. Xue,
Yulei Zhao,
Piro Lito
Publication year - 2021
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.abf1730
Subject(s) - gtpase , kras , gtpase activating protein , guanosine , guanosine triphosphate , microbiology and biotechnology , g protein , guanine nucleotide exchange factor , gtp' , gtp binding protein regulators , biochemistry , signal transduction , chemistry , mutant , small gtpase , biology , guanosine diphosphate , cancer research , mutation , enzyme , gene
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 KRASG12C 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. Liet 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
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