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

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

Blog Article

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 ECHINACEA 2+ 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 Ni-MH/Ni-Cd 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.