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Cell Cycle Regulation by the Nutrient-Sensing Mammalian Target of Rapamycin (mTOR) Pathway

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Cell Cycle Control

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1170))

Abstract

Cell division involves a series of ordered and controlled events that lead to cell proliferation. Cell cycle progression implies not only demanding amounts of cell mass, protein, lipid, and nucleic acid content but also a favorable energy state. The mammalian target of rapamycin (mTOR), in response to the energy state, nutrient status, and growth factor stimulation of cells, plays a pivotal role in the coordination of cell growth and the cell cycle. Here, we review how the nutrient-sensing mTOR-signaling cascade molecularly integrates nutritional and mitogenic/anti-apoptotic cues to accurately coordinate cell growth and cell cycle. First, we briefly outline the structure, functions, and regulation of the mTOR complexes (mTORC1 and mTORC2). Second, we concisely evaluate the best known ability of mTOR to control G1-phase progression. Third, we discuss in detail the recent evidence that indicates a new genome stability caretaker function of mTOR based on the specific ability of phosphorylated forms of several mTOR-signaling components (AMPK, raptor, TSC, mTOR, and S6K1), which spatially and temporally associate with essential mitotic regulators at the mitotic spindle and at the cytokinetic cleavage furrow.

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Acknowledgements

This work was supported financially by grants CP05-00090, PI06-0778, and RD06-0020-0028 from the Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo, Fondo de Investigación Sanitaria (FIS), Spain; the Fundación Científica de la Asociación Española Contra el Cáncer (AECC, Spain); and the Ministerio de Ciencia e Innovación (SAF2009-11579 and SAF2012-389134, Plan Nacional de I + D + I, MICINN, Spain).

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Authors and Affiliations

  1. Metabolism & Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology, Girona (ICO-Girona), Hospital Dr. Josep Trueta de Girona, Ctra. França s/n, E-17007, Girona, Catalonia, Spain

    Elisabet Cuyàs, Bruna Corominas-Faja & Javier A. Menendez

  2. Unitat de Recerca Biomèdica (URB-CRB), Institut d’Investigació Sanitaria Pere i Virgili (IISPV), Universitat Rovira i Virgili, Reus, Catalonia, Spain

    Jorge Joven

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  1. Elisabet Cuyàs
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  2. Bruna Corominas-Faja
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  3. Jorge Joven
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  4. Javier A. Menendez
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  1. Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Eishi Noguchi

  2. Dept of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, USA

    Mariana C. Gadaleta

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Cuyàs, E., Corominas-Faja, B., Joven, J., Menendez, J.A. (2014). Cell Cycle Regulation by the Nutrient-Sensing Mammalian Target of Rapamycin (mTOR) Pathway. In: Noguchi, E., Gadaleta, M. (eds) Cell Cycle Control. Methods in Molecular Biology, vol 1170. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0888-2_7

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  • DOI: https://doi.org/10.1007/978-1-4939-0888-2_7

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