RGS7 is recurrently mutated in melanoma and promotes migration and invasion of human cancer cells.

ABSTRACT: Analysis of 501 melanoma exomes revealed RGS7, which encodes a GTPase-accelerating protein (GAP), to be a tumor-suppressor gene. RGS7 was mutated in 11% of melanomas and was found to harbor three recurrent mutations (p.R44C, p.E383K and p.R416Q). Structural modeling of the most common recurrent mutation of the three (p.R44C) predicted that it destabilizes the protein due to the loss of an H-bond and salt bridge network between the mutated position and the serine and aspartic acid residues at positions 58 as 61, respectively. We experimentally confirmed this prediction showing that the p.R44C mutant protein is indeed destabilized. We further show RGS7 p.R44C has weaker catalytic activity for its substrate Gα_o, thus providing a dual mechanism for its loss of function. Both of thes

SUBMITTER: Qutob N 

PROVIDER: S-EPMC5766496 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature