title: mTORC1 and p53: clash of the gods?
abstract: A balance must be struck between cell growth and stress responses to ensure that cells proliferate without accumulating damaged DNA. This balance means that optimal cell proliferation requires the integration of pro-growth and stress-response pathways. mTOR (mechanistic target of rapamycin) is a pleiotropic kinase found in complex 1 (mTORC1).The mTORC1 pathway governs a response to mitogenic signals with high energy levels to promote protein synthesis and cell growth. In contrast, the p53DNA damage response pathway is the arbiter of cell proliferation, restraining mTORC1 under conditions of genotoxic stress. Recent studies suggest a complicated integration of these pathways to ensure successful cell growth and proliferation without compromising genome maintenance. Deciphering this integration could be key to understanding the potential clinical usefulness of mTORC1 inhibitors like rapamycin. Here we discuss how these p53-mTORC1 interactions might play a role in the suppression of cancer and perhaps the development of cellular senescence and organismal aging.
authors.affiliation: Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center, San Antonio, TX, USA. hastye@uthscsa.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Hasty
authors.forename: Zelton Dave
authors.initials: ZD
authors.lastname: Sharp
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
mesh_terms: D000375:Aging; D004260:DNA Repair; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D016159:Tumor Suppressor Protein p53; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D048308:Mitogen-Activated Protein Kinase 14