TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells

Chihiro Yamada; Aya Morooka; Seira Miyazaki; Masayoshi Nagai; Satoru Mase; Kenji Iemura; Most Naoshia Tasnin; Tsuneyuki Takuma; Shotaro Nakamura; Shamsul Morshed; Naoki Koike; Md. Golam Mostofa; Muhammad Arifur Rahman; Tasnuva Sharmin; Haruko Katsuta; Kotaro Ohara; Kozo Tanaka; Takashi Ushimaru

iScience (Feb 2022)

TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells

Chihiro Yamada,
Aya Morooka,
Seira Miyazaki,
Masayoshi Nagai,
Satoru Mase,
Kenji Iemura,
Most Naoshia Tasnin,
Tsuneyuki Takuma,
Shotaro Nakamura,
Shamsul Morshed,
Naoki Koike,
Md. Golam Mostofa,
Muhammad Arifur Rahman,
Tasnuva Sharmin,
Haruko Katsuta,
Kotaro Ohara,
Kozo Tanaka,
Takashi Ushimaru

Affiliations

Chihiro Yamada: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan
Aya Morooka: Department of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan
Seira Miyazaki: Department of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan
Masayoshi Nagai: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan; Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Satoru Mase: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan
Kenji Iemura: Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Most Naoshia Tasnin: Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan
Tsuneyuki Takuma: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan
Shotaro Nakamura: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan
Shamsul Morshed: Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan
Naoki Koike: Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan
Md. Golam Mostofa: Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan
Muhammad Arifur Rahman: Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan
Tasnuva Sharmin: Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan
Haruko Katsuta: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan
Kotaro Ohara: Department of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan
Kozo Tanaka: Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Takashi Ushimaru: Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, Japan; Department of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan; Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan; Corresponding author

Journal volume & issue: Vol. 25, no. 2
p. 103675

Abstract

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Summary: Unsatisfied kinetochore-microtubule attachment activates the spindle assembly checkpoint to inhibit the metaphase-anaphase transition. However, some cells eventually override mitotic arrest by mitotic slippage. Here, we show that inactivation of TORC1 kinase elicits mitotic slippage in budding yeast and human cells. Yeast mitotic slippage was accompanied with aberrant aspects, such as degradation of the nucleolar protein Net1, release of phosphatase Cdc14, and anaphase-promoting complex/cyclosome (APC/C)-Cdh1-dependent degradation of securin and cyclin B in metaphase. This mitotic slippage caused chromosome instability. In human cells, mammalian TORC1 (mTORC1) inactivation also invoked mitotic slippage, indicating that TORC1 inactivation-induced mitotic slippage is conserved from yeast to mammalian cells. However, the invoked mitotic slippage in human cells was not dependent on APC/C-Cdh1. This study revealed an unexpected involvement of TORC1 in mitosis and provides information on undesirable side effects of the use of TORC1 inhibitors as immunosuppressants and anti-tumor drugs.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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