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Mammalian target of rapamycin complex 1: signalling inputs, substrates and feedback mechanisms

E A Dunlop1, A R Tee

  • 1Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, Wales, UK.

Cellular Signalling
|January 27, 2009
PubMed

Insights

The mammalian target of rapamycin (mTOR) pathway, particularly mTORC1 signaling, is crucial in cancer and cell growth. Recent updates reveal new targets and regulators, expanding our understanding of its complex roles.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The mammalian target of rapamycin (mTOR) signaling pathway is involved in cancer and inherited hamartoma syndromes.
  • mTOR inhibitors like rapamycin are in clinical trials.
  • Knowledge of the mTOR pathway is rapidly expanding.

Purpose of the Study:

  • To provide an update on recent additions to the mTOR pathway.
  • To emphasize mTORC1 signaling, its novel functions, and regulators.
  • To discuss upstream mechanisms controlling mTORC1.

Main Methods:

  • Literature review of recent research on the mTOR pathway.
  • Focus on mTORC1 signaling mechanisms and targets.
  • Analysis of upstream regulators and associated proteins.

Main Results:

  • Novel mTORC1 signaling mechanisms modulate mitochondrial biogenesis, hypoxia signaling, and cell cycle progression.
  • New mTORC1 targets identified include YY1, HIF, and SGK1.
  • Novel mTORC1-associated proteins like PRAS40, FKBP38, Rag GTPases, and RalA have been uncovered.

Conclusions:

  • mTORC1 signaling has multifaceted roles in cell growth, proliferation, and newly identified functions.
  • Understanding upstream regulators (hypoxia, energy, nutrients) and associated proteins is key to controlling mTORC1 activity.
  • This review highlights significant recent advances in mTOR pathway research.

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