mTORC1 and p53 |
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Authors: | Paul Hasty Zelton Dave Sharp Tyler J Curiel Judith Campisi |
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Institution: | 1.Department of Molecular Medicine and Institute of Biotechnology; University of Texas Health Science Center; San Antonio, TX USA;2.Department of Medicine; University of Texas Health Science Center; San Antonio, TX USA;3.Cancer Therapy and Research Center; University of Texas Health Science Center; San Antonio, TX USA;4.Buck Institute for Research on Aging; Novato CA USA;5.Lawrence Berkeley National Laboratory; Berkeley, CA USA |
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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 p53 DNA 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. |
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Keywords: | aging cancer cellular senescence mTORC1 p53 |
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