Rapamycin-sensitive mechanisms confine the growth of fission yeast below the temperatures detrimental to cell physiology
Yuichi Morozumi,
Fontip Mahayot,
Yukiko Nakase,
Jia Xin Soong,
Sayaka Yamawaki,
Fajar Sofyantoro,
Yuki Imabata,
Arisa H. Oda,
Miki Tamura,
Shunsuke Kofuji,
Yutaka Akikusa,
Ayu Shibatani,
Kunihiro Ohta,
Kazuhiro Shiozaki
Affiliations
Yuichi Morozumi
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan; Corresponding author
Fontip Mahayot
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Yukiko Nakase
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Jia Xin Soong
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Sayaka Yamawaki
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Fajar Sofyantoro
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan; Faculty of Biology, Universitas Gadjah Mada, Sleman, Yogyakarta 55281, Indonesia
Yuki Imabata
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Arisa H. Oda
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan
Miki Tamura
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan
Shunsuke Kofuji
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Yutaka Akikusa
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Ayu Shibatani
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
Kunihiro Ohta
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan
Kazuhiro Shiozaki
Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan; Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA 95616, USA
Summary: 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.