TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells.
Biological sciences
Cell biology
Molecular biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
18 Feb 2022
18 Feb 2022
Historique:
received:
28
12
2020
revised:
20
10
2021
accepted:
20
12
2021
entrez:
10
2
2022
pubmed:
11
2
2022
medline:
11
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35141499
doi: 10.1016/j.isci.2021.103675
pii: S2589-0042(21)01645-X
pmc: PMC8814761
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103675Informations de copyright
© 2021.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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