Work

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

Year: 2021

Type: article

Abstract: 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

Source: Science

DOI: 10.1126/science.abf1730

Authors: Chuanchuan Li, Alberto Vides, Dongsung Kim, Jenny Y. Xue, Yulei Zhao, Piro Lito

Institutions: Memorial Sloan Kettering Cancer Center, Rockefeller University, Weill Cornell Medicine

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Cancer Institute

Awards: G3254162575, G3586869972, G6065333432, Cancer Center Support Grant, Dissecting KRAS oncoprotein signaling with small molecule inhibitors