title: The p53 tumor suppressor targets a novel regulator of G protein signaling.
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 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.
authors.affiliation: Department of Molecular Genetics, Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543, USA.
authors.forename: L
authors.initials: L
authors.lastname: Buckbinder
authors.forename: S
authors.initials: S
authors.lastname: Velasco-Miguel
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Xu
authors.forename: R
authors.initials: R
authors.lastname: Talbott
authors.forename: L
authors.initials: L
authors.lastname: Gelbert
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: B R
authors.initials: BR
authors.lastname: Seizinger
authors.forename: J S
authors.initials: JS
authors.lastname: Gutkind
authors.forename: N
authors.initials: N
authors.lastname: Kley
mesh_terms: 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
chemical_list: D018076:DNA, Complementary; D011506:Proteins; D020710:RGS Proteins; C107413:RGS16 protein; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D019204:GTP-Binding Proteins