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Gene-targeted Random Mutagenesis to Select Heterochromatin-destabilizing Proteasome Mutants in Fission Yeast
Published on: May 15, 2018
The fission yeast TOR proteins and the rapamycin response: an unexpected tale
1Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel-Aviv University, 69978 Tel-Aviv, Israel. ronitt@post.tau.ac.il
Abstract:
The TOR proteins are known as key regulators of cell growth in response to nutritional and mitogenic signals and as targets for the immunosuppressive and anti-cancerous drug rapamycin. The fission yeast Schizosaccharomyces pombe has two TOR homologues, tor1+ and tor2+. Despite their structural similarity, these genes have distinct functions: tor1+ is required under starvation, extreme temperatures, and osmotic or oxidative stress conditions, whereas tor2+ is required under normal growth conditions. Surprisingly, rapamycin does not seem to inhibit the S. pombe TOR-related functions. Rapamycin specifically inhibits sexual development in S. pombe, and this seems to stem from direct inhibition of the S. pombe FKBP12 homologue. Why S. pombe cells are resistant to rapamycin during the growth phase is as yet unclear and awaits further analysis of the TOR-dependent signaling pathways.
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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