1. Rapamycin-sensitive mechanisms confine the growth of fission yeast below the temperatures detrimental to cell physiology
- Author
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Morozumi, Yuichi, Mahayot, Fontip, Nakase, Yukiko, Soong, Jia Xin, Yamawaki, Sayaka, Sofyantoro, Fajar, Imabata, Yuki, Oda, Arisa H, Tamura, Miki, Kofuji, Shunsuke, Akikusa, Yutaka, Shibatani, Ayu, Ohta, Kunihiro, and Shiozaki, Kazuhiro
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Generic health relevance ,Biological sciences ,Microbial physiology ,Microbiology ,Molecular microbiology - Abstract
Cells cease to proliferate above their growth-permissible temperatures, a ubiquitous phenomenon generally attributed to heat damage to cellular macromolecules. We here report that, in the presence of rapamycin, a potent inhibitor of Target of Rapamycin Complex 1 (TORC1), the fission yeast Schizosaccharomyces pombe can proliferate at high temperatures that usually arrest its growth. Consistently, mutations to the TORC1 subunit RAPTOR/Mip1 and the TORC1 substrate Sck1 significantly improve cellular heat resistance, suggesting that TORC1 restricts fission yeast growth at high temperatures. Aiming for a more comprehensive understanding of the negative regulation of high-temperature growth, we conducted genome-wide screens, which identified additional factors that suppress cell proliferation at high temperatures. Among them is Mks1, which is phosphorylated in a TORC1-dependent manner, forms a complex with the 14-3-3 protein Rad24, and suppresses the high-temperature growth independently of Sck1. Our study has uncovered unexpected mechanisms of growth restraint even below the temperatures deleterious to cell physiology.
- Published
- 2024