Research ResourceBiochemistry

Probing the mutational landscape of regulators of G protein signaling proteins in cancer

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Science Signaling  04 Feb 2020:
Vol. 13, Issue 617, eaax8620
DOI: 10.1126/scisignal.aax8620

Impairing RGS protein function

Mutations in the genes encoding the α subunits of heterotrimeric G proteins are associated with cancer. In particular, mutations that prevent the Gα subunits from hydrolyzing GTP, thus rendering them constitutively active, are pro-oncogenic. DiGiacomo et al. surveyed cancer-associated mutations in regulator of G protein signaling (RGS) proteins, which are physiological inhibitors of G proteins. Through bioinformatics analysis, genetic interaction studies in yeast, and functional assays in mammalian cells, the authors showed that many cancer-associated RGS mutants fail to inhibit G protein signaling because of reduced protein stability or impaired interactions with their targets. With these tools, further cancer-associated mutations in RGS proteins can be characterized.

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