Mitotic slippage is determined by p31.sup.comet and the weakening of the spindle-assembly checkpoint

Mitotic slippage involves cells exiting mitosis without proper chromosome segregation. Although degradation of cyclin B1 during prolonged mitotic arrest is believed to trigger mitotic slippage, its upstream regulation remains obscure. Whether mitotic slippage is caused by APC/C.sup.CDC20 activity th...

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Veröffentlicht in:Oncogene 2020-03, Vol.39 (13), p.2819
Hauptverfasser: Lok, Tsun Ming, Wang, Yang, Xu, Wendy Kaichun, Xie, Siwei, Ma, Hoi Tang, Poon, Randy Y. C
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container_issue 13
container_start_page 2819
container_title Oncogene
container_volume 39
creator Lok, Tsun Ming
Wang, Yang
Xu, Wendy Kaichun
Xie, Siwei
Ma, Hoi Tang
Poon, Randy Y. C
description Mitotic slippage involves cells exiting mitosis without proper chromosome segregation. Although degradation of cyclin B1 during prolonged mitotic arrest is believed to trigger mitotic slippage, its upstream regulation remains obscure. Whether mitotic slippage is caused by APC/C.sup.CDC20 activity that is able to escape spindle-assembly checkpoint (SAC)-mediated inhibition, or is actively promoted by a change in SAC activity remains an outstanding issue. We found that a major culprit for mitotic slippage involves reduction of MAD2 at the kinetochores, resulting in a progressive weakening of SAC during mitotic arrest. A further level of control of the timing of mitotic slippage is through p31.sup.comet-mediated suppression of MAD2 activation. The loss of kinetochore MAD2 was dependent on APC/C.sup.CDC20, indicating a feedback control of APC/C to SAC during prolonged mitotic arrest. The gradual weakening of SAC during mitotic arrest enables APC/C.sup.CDC20 to degrade cyclin B1, cumulating in the cell exiting mitosis by mitotic slippage.
doi_str_mv 10.1038/s41388-020-1187-6
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subjects Cyclins
Enzymes
Gene expression
Genetic aspects
Health aspects
Mitosis
Regulation
title Mitotic slippage is determined by p31.sup.comet and the weakening of the spindle-assembly checkpoint
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