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Dysregulation of the TSC-mTOR pathway in human disease

Nature Genetics volume 37, pages 19–24 (2005)Cite this article

Abstract

The mammalian target of rapamycin (mTOR) has a central role in the regulation of cell growth. mTOR receives input from multiple signaling pathways, including growth factors and nutrients, to stimulate protein synthesis by phosphorylating key translation regulators such as ribosomal S6 kinase and eukaryote initiation factor 4E binding protein 1. High levels of dysregulated mTOR activity are associated with several hamartoma syndromes, including tuberous sclerosis complex, the PTEN-related hamartoma syndromes and Peutz-Jeghers syndrome. These disorders are all caused by mutations in tumor-suppressor genes that negatively regulate mTOR. Here we discuss the emerging evidence for a functional relationship between the mTOR signaling pathway and several genetic diseases, and we present evidence supporting a model in which dysregulation of mTOR may be a common molecular basis, not only for hamartoma syndromes, but also for other cellular hypertrophic disorders.

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Figure 1: mTOR signaling in the regulation of translation.
Figure 2: The molecular link between several inherited human diseases.

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Acknowledgements

We thank D. Ginsburg, J. Bernat, C-H. Lee and the members of the laboratory of K.-L.G. for critical reading of the manuscript and for discussions. We apologize to those colleagues whose work could not be cited in this review owing to space limitations. M.N.C. is funded by a fellowship from the Program in Organogenesis, and the work of the authors is supported by grants from the Walther Cancer Institute and the National Institutes of Health.

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  1. Ken Inoki and Michael N Corradetti: These authors contributed equally to this work.

Authors and Affiliations

  1. Life Sciences Institute, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Ken Inoki, Michael N Corradetti & Kun-Liang Guan

  2. Department of Biological Chemistry, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Kun-Liang Guan

  3. Institute of Gerontology, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Kun-Liang Guan

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Inoki, K., Corradetti, M. & Guan, KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 37, 19–24 (2005). https://doi.org/10.1038/ng1494

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