Dysregulation of the TSC-mTOR pathway in human disease

Nat Genet. 2005 Jan;37(1):19-24. doi: 10.1038/ng1494.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Autophagy / physiology
  • Cardiomegaly / enzymology
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • Hamartoma / enzymology
  • Hamartoma / genetics
  • Hamartoma / metabolism
  • Humans
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • TOR Serine-Threonine Kinases
  • Tuberous Sclerosis / enzymology
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / metabolism*


  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases