TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells
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 budd...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422101645X |
| _version_ | 1819289175720984576 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chihiro Yamada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T03:02:40Z |
| format | Article |
| id | doaj.art-1022385d83204cfdbe69989bb4c99062 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-24T03:02:40Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1022385d83204cfdbe69989bb4c990622022-12-21T17:18:09ZengElsevieriScience2589-00422022-02-01252103675TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cellsChihiro Yamada0Aya Morooka1Seira Miyazaki2Masayoshi Nagai3Satoru Mase4Kenji Iemura5Most Naoshia Tasnin6Tsuneyuki Takuma7Shotaro Nakamura8Shamsul Morshed9Naoki Koike10Md. Golam Mostofa11Muhammad Arifur Rahman12Tasnuva Sharmin13Haruko Katsuta14Kotaro Ohara15Kozo Tanaka16Takashi Ushimaru17Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, JapanDepartment of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, JapanDepartment of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, JapanDepartment 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, JapanDepartment of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, JapanDepartment of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanGraduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, JapanDepartment of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, JapanDepartment of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, JapanGraduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, JapanGraduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, JapanGraduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, JapanGraduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, JapanGraduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, JapanDepartment of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8021, JapanDepartment of Biological Science, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, JapanDepartment of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, JapanDepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422101645XBiological sciencesMolecular biologyCell biology |
| spellingShingle | 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 TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells iScience Biological sciences Molecular biology Cell biology |
| title | TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells |
| title_full | TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells |
| title_fullStr | TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells |
| title_full_unstemmed | TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells |
| title_short | TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells |
| title_sort | torc1 inactivation promotes apc c dependent mitotic slippage in yeast and human cells |
| topic | Biological sciences Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422101645X |
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