The p53 tumor suppressor targets a novel regulator of G protein signaling

The p53 tumor suppressor targets a novel regulator of G protein signaling

^*Department of Molecular Genetics and ^‡Biomolecular Drug Discovery, Oncology, Bristol–Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543; and ^†Molecular Signaling Unit, Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892

Abstract

Heterotrimeric G proteins transduce multiple growth-factor-receptor-initiated and intracellular signals that may lead to activation of the mitogen-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 proposed GTPase-activating protein activity. Overexpression of A28-RGS14p protein inhibits both G_i- and G_q-coupled growth-factor-receptor-mediated activation of the mitogen-activated protein kinase signaling pathway in mammalian cells. Thus, through the induction of A28-RGS14, p53 may regulate cellular sensitivity to growth and/or survival factors acting through G protein-coupled receptor pathways.

Footnotes

↵ § Current address: Genome Therapeutics Corporation, Waltham, MA 02154.
↵ ¶ To whom reprint requests should be addressed.e-mail.Kley{at}genomecorp.com.
Thomas E. Shenk, Princeton University, Princeton, NJ
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. U70426 and U70427).
ABBREVIATIONS:

MAPK,

mitogen-activated protein kinase;

RGS,

regulators of G protein signaling;

HA,

hemagglutinin