The TOR signalling network from yeast to man

Claudio De Virgilio1, Robbie Loewith

  • 1Department of Microbiology and Molecular Medicine, University of Geneva, 1211 Geneva 4, Switzerland. Claudio.DeVirgilio@medecine.unige.ch

Insights

The target of rapamycin (TOR) pathway, crucial for cell growth and metabolism, involves two complexes. Aberrant TOR complex 1 signaling is linked to diseases like cancer, with rapamycin efficacy under clinical evaluation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The target of rapamycin (TOR) is a vital serine/threonine protein kinase conserved across species.
  • TOR functions within two distinct multiprotein complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2).
  • TORC1 is rapamycin-sensitive and regulates cellular metabolism in response to growth cues, while TORC2, insensitive to rapamycin, controls spatial growth aspects like cell polarity.

Purpose of the Study:

  • To explore the TOR signaling network, focusing on components upstream of TORC1.
  • To understand the role of TOR signaling in various pathologies, including metabolic diseases and cancers.
  • To evaluate the therapeutic potential of rapamycin and related drugs in treating TOR-associated diseases.

Main Methods:

  • Utilized diverse model systems, including flies and mammalian tissue culture cells.
  • Investigated signaling components upstream of TORC1.
  • Reviewed recent studies on TOR signaling pathways and their implications.

Main Results:

  • Elucidated numerous signaling components upstream of TORC1 through studies in model organisms.
  • Demonstrated that aberrant mammalian TORC1 signaling contributes to metabolic diseases, hyperproliferative disorders, and cancers.
  • Identified rapamycin and related compounds as potential therapeutic agents for these pathologies.

Conclusions:

  • TOR signaling is a fundamental pathway with conserved functions from yeast to humans.
  • Dysregulation of TORC1 signaling is implicated in significant human diseases.
  • Clinical trials are underway to assess the efficacy of rapamycin-based therapies for TOR-related pathologies.

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