mTOR-dependent cell survival mechanisms

Cold Spring Harb Perspect Biol. 2012 Dec 1;4(12):a008771. doi: 10.1101/cshperspect.a008771.

Abstract

The mechanistic target of rapamycin (mTOR) kinase is a conserved regulator of cell growth, proliferation, and survival. In cells, mTOR is the catalytic subunit of two complexes called mTORC1 and mTORC2, which have distinct upstream regulatory signals and downstream substrates. mTORC1 directly senses cellular nutrient availability while indirectly sensing circulating nutrients through growth factor signaling pathways. Cellular stresses that restrict growth also impinge on mTORC1 activity. mTORC2 is less well understood and appears only to sense growth factors. As an integrator of diverse growth regulatory signals, mTOR evolved to be a central signaling hub for controlling cellular metabolism and energy homoeostasis, and defects in mTOR signaling are important in the pathologies of cancer, diabetes, and aging. Here we discuss mechanisms by which each mTOR complex might regulate cell survival in response to metabolic and other stresses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Cell Growth Processes / physiology*
  • Cell Survival / physiology*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Multiprotein Complexes / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / metabolism*
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / metabolism

Substances

  • Multiprotein Complexes
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2