The p53 tumor suppressor targets a novel regulator of G protein signaling.
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 Gi- and Gq-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.
Buckbinder
L
L
Department of Molecular Genetics, Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543, USA.
Velasco-Miguel
S
S
Chen
Y
Y
Xu
N
N
Talbott
R
R
Gelbert
L
L
Gao
J
J
Seizinger
B R
BR
Gutkind
J S
JS
Kley
N
N
D000595:Amino Acid Sequence; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020710:RGS Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018076:DNA, Complementary; D011506:Proteins; D020710:RGS Proteins; C107413:RGS16 protein; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D019204:GTP-Binding Proteins