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mTORC1: A Signaling Integration Node Involved in Cell Growth

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mTOR Pathway and mTOR Inhibitors in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The mammalian target of rapamycin (mTOR) is an atypical serine/threonine kinase that plays an indispensable role in the control of cell growth. When localized with the interacting proteins raptor and mLST8 in the mammalian target of rapamycin complex 1 (mTORC1), mTOR serves as an integrator of cellular signals to control the balance between cellular anabolism and cellular catabolism. Under conditions that promote cell growth, or in the presence of common genetic lesions associated with cancer, mTORC1 signals to the effectors 4E-BP1 and S6K1 resulting in ribosomal biogenesis and enhanced mRNA translation. The positive effects of mTORC1 on mRNA translation involve a dynamic molecular process that results in an increase in bulk protein synthesis, including more dramatic effects on a subset of mRNA species encoding pro-growth, anti-apoptotic proteins. Recent data also suggest a role of mTORC1 in the “pioneer” round of mRNA translation, in addition to the more established effects on “steady-state” protein biosynthesis. Growth control by mTORC1 is required in physiological and developmental settings for proper maintenance of cellular homeostasis, cell survival, and embryonic development, while inappropriate regulation of mTORC1 signaling is observed in the overwhelming majority of human cancers. This review will discuss the current view of the signaling network upstream of mTORC1 and the regulation of protein biosynthesis by this evolutionarily conserved, clinically relevant cell signaling node.

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  1. Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA

    Neil Kubica & John Blenis

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    Vitaly A. Polunovsky

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    Peter J. Houghton

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Kubica, N., Blenis, J. (2009). mTORC1: A Signaling Integration Node Involved in Cell Growth. In: Polunovsky, V., Houghton, P. (eds) mTOR Pathway and mTOR Inhibitors in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-271-1_1

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