Dysregulation of the TSC-mTOR pathway in human disease.


Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Inoki, K; Corradetti, MN; Guan, K-L

Published Date

  • January 2005

Published In

Volume / Issue

  • 37 / 1

Start / End Page

  • 19 - 24

PubMed ID

  • 15624019

Pubmed Central ID

  • 15624019

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng1494


  • eng

Conference Location

  • United States