THE P53 TUMOR-SUPPRESSOR TARGETS A NOVEL REGULATOR OF G-PROTEIN SIGNALING

Heterotrimeric G proteins transduce multiple growth-factor-receptor-in itiated and intracellular signals that may lead to activation of the m itogen-activated or stress-activated protein kinases, Herein we report on the identification of a novel p53 target gene (A28-RGS14) that is induced in response to genotoxic stress and encodes a novel member of a family of regulators of G protein signaling (RGS) proteins with prop osed GTPase-activating protein activity. Overexpression of A28-RGS14p protein inhibits both G(i)- and G(q)-coupled growth-factor-receptor-me diated activation of the mitogen-activated protein kinase signaling pa thway in mammalian cells. Thus, through the induction of A28-RGS14, p5 3 may regulate cellular sensitivity to growth and/or survival factors acting through G protein-coupled receptor pathways.