The fission yeast TOR proteins and the rapamycin response: an unexpected tale

R Weisman1

  • 1Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv, Israel. ronitt@post.tau.ac.il

Insights

Fission yeast TOR proteins regulate cell growth. Unlike other organisms, rapamycin inhibits sexual development in S. pombe but not growth, suggesting unique resistance mechanisms.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Yeast Genetics

Background:

  • Target of Rapamycin (TOR) proteins are crucial for cell growth regulation in response to nutrients and growth factors.
  • TOR proteins are targeted by the immunosuppressive and anti-cancer drug rapamycin.
  • Fission yeast Schizosaccharomyces pombe possesses two TOR homologues, tor1+ and tor2+, with distinct roles.

Purpose of the Study:

  • To investigate the functions of TOR homologues in Schizosaccharomyces pombe.
  • To understand the differential effects of rapamycin on S. pombe growth and sexual development.
  • To explore the mechanisms behind S. pombe resistance to rapamycin during growth.

Main Methods:

  • Comparative analysis of tor1+ and tor2+ functions under various stress conditions.
  • Assessment of rapamycin's impact on S. pombe growth and sexual differentiation.
  • Investigation of FKBP12 homologue's role in rapamycin sensitivity.

Main Results:

  • tor1+ is essential for survival under starvation, extreme temperatures, and osmotic/oxidative stress.
  • tor2+ is required for normal growth conditions.
  • Rapamycin inhibits sexual development in S. pombe, likely via FKBP12 inhibition, but does not affect growth.
  • S. pombe exhibits resistance to rapamycin during the growth phase.

Conclusions:

  • TOR proteins in S. pombe have distinct, condition-specific roles.
  • Rapamycin's inhibitory effect on S. pombe sexual development is separable from its growth-inhibitory function in other organisms.
  • The resistance of S. pombe to rapamycin during growth warrants further investigation into TOR-dependent signaling pathways.

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