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Mitotic slippage is determined by p31(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(CDC20) activity that...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098889/ https://www.ncbi.nlm.nih.gov/pubmed/32029899 http://dx.doi.org/10.1038/s41388-020-1187-6 |
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author | Lok, Tsun Ming Wang, Yang Xu, Wendy Kaichun Xie, Siwei Ma, Hoi Tang Poon, Randy Y. C. |
author_facet | Lok, Tsun Ming Wang, Yang Xu, Wendy Kaichun Xie, Siwei Ma, Hoi Tang Poon, Randy Y. C. |
author_sort | Lok, Tsun Ming |
collection | PubMed |
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(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(comet)-mediated suppression of MAD2 activation. The loss of kinetochore MAD2 was dependent on APC/C(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(CDC20) to degrade cyclin B1, cumulating in the cell exiting mitosis by mitotic slippage. |
format | Online Article Text |
id | pubmed-7098889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70988892020-03-30 Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint Lok, Tsun Ming Wang, Yang Xu, Wendy Kaichun Xie, Siwei Ma, Hoi Tang Poon, Randy Y. C. Oncogene Article 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(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(comet)-mediated suppression of MAD2 activation. The loss of kinetochore MAD2 was dependent on APC/C(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(CDC20) to degrade cyclin B1, cumulating in the cell exiting mitosis by mitotic slippage. Nature Publishing Group UK 2020-02-06 2020 /pmc/articles/PMC7098889/ /pubmed/32029899 http://dx.doi.org/10.1038/s41388-020-1187-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lok, Tsun Ming Wang, Yang Xu, Wendy Kaichun Xie, Siwei Ma, Hoi Tang Poon, Randy Y. C. Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
title | Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
title_full | Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
title_fullStr | Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
title_full_unstemmed | Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
title_short | Mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
title_sort | mitotic slippage is determined by p31(comet) and the weakening of the spindle-assembly checkpoint |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098889/ https://www.ncbi.nlm.nih.gov/pubmed/32029899 http://dx.doi.org/10.1038/s41388-020-1187-6 |
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