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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
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
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
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
format Article
fullrecord <record><control><sourceid>gale</sourceid><recordid>TN_cdi_gale_infotracmisc_A618688990</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A618688990</galeid><sourcerecordid>A618688990</sourcerecordid><originalsourceid>FETCH-LOGICAL-g670-9b9db0b9b66b6f97fe7d2b0ea78333c639a800a8a85d53c72cccf494eb77ace13</originalsourceid><addsrcrecordid>eNptjk1LAzEYhHNQsFZ_gLeA513fbNp8HEvxo1Dx0nvJx5tt7G52aSLSf--iHjzIHAaGZ4Yh5I5BzYCrh7xgXKkKGqgYU7ISF2QGegmVbnhzRa5zfgcAqaGZEf8ay1Cio7mL42hapDFTjwVPfUzoqT3TkbM6f4y1G3os1CRPywHpJ5ojpphaOoTvII8x-Q4rkzP2tjtTd0B3HIeYyg25DKbLePvrc7J7etytX6rt2_NmvdpWrZDTO6u9BautEFYELQNK31hAIxXn3AmujQIwyqilX3InG-dcWOgFWimNQ8bn5P5ntjUd7mMKQzkZ18fs9ivBlFBKa5io-h9qksc-uiFhiFP-p_AFMJhmvw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Mitotic slippage is determined by p31.sup.comet and the weakening of the spindle-assembly checkpoint</title><source>Alma/SFX Local Collection</source><creator>Lok, Tsun Ming ; Wang, Yang ; Xu, Wendy Kaichun ; Xie, Siwei ; Ma, Hoi Tang ; Poon, Randy Y. C</creator><creatorcontrib>Lok, Tsun Ming ; Wang, Yang ; Xu, Wendy Kaichun ; Xie, Siwei ; Ma, Hoi Tang ; Poon, Randy Y. C</creatorcontrib><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.</description><identifier>ISSN: 0950-9232</identifier><identifier>DOI: 10.1038/s41388-020-1187-6</identifier><language>eng</language><publisher>Nature Publishing Group</publisher><subject>Cyclins ; Enzymes ; Gene expression ; Genetic aspects ; Health aspects ; Mitosis ; Regulation</subject><ispartof>Oncogene, 2020-03, Vol.39 (13), p.2819</ispartof><rights>COPYRIGHT 2020 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids></links><search><creatorcontrib>Lok, Tsun Ming</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Xu, Wendy Kaichun</creatorcontrib><creatorcontrib>Xie, Siwei</creatorcontrib><creatorcontrib>Ma, Hoi Tang</creatorcontrib><creatorcontrib>Poon, Randy Y. C</creatorcontrib><title>Mitotic slippage is determined by p31.sup.comet and the weakening of the spindle-assembly checkpoint</title><title>Oncogene</title><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.</description><subject>Cyclins</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Mitosis</subject><subject>Regulation</subject><issn>0950-9232</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptjk1LAzEYhHNQsFZ_gLeA513fbNp8HEvxo1Dx0nvJx5tt7G52aSLSf--iHjzIHAaGZ4Yh5I5BzYCrh7xgXKkKGqgYU7ISF2QGegmVbnhzRa5zfgcAqaGZEf8ay1Cio7mL42hapDFTjwVPfUzoqT3TkbM6f4y1G3os1CRPywHpJ5ojpphaOoTvII8x-Q4rkzP2tjtTd0B3HIeYyg25DKbLePvrc7J7etytX6rt2_NmvdpWrZDTO6u9BautEFYELQNK31hAIxXn3AmujQIwyqilX3InG-dcWOgFWimNQ8bn5P5ntjUd7mMKQzkZ18fs9ivBlFBKa5io-h9qksc-uiFhiFP-p_AFMJhmvw</recordid><startdate>20200326</startdate><enddate>20200326</enddate><creator>Lok, Tsun Ming</creator><creator>Wang, Yang</creator><creator>Xu, Wendy Kaichun</creator><creator>Xie, Siwei</creator><creator>Ma, Hoi Tang</creator><creator>Poon, Randy Y. C</creator><general>Nature Publishing Group</general><scope/></search><sort><creationdate>20200326</creationdate><title>Mitotic slippage is determined by p31.sup.comet and the weakening of the spindle-assembly checkpoint</title><author>Lok, Tsun Ming ; Wang, Yang ; Xu, Wendy Kaichun ; Xie, Siwei ; Ma, Hoi Tang ; Poon, Randy Y. C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g670-9b9db0b9b66b6f97fe7d2b0ea78333c639a800a8a85d53c72cccf494eb77ace13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cyclins</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Mitosis</topic><topic>Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lok, Tsun Ming</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Xu, Wendy Kaichun</creatorcontrib><creatorcontrib>Xie, Siwei</creatorcontrib><creatorcontrib>Ma, Hoi Tang</creatorcontrib><creatorcontrib>Poon, Randy Y. C</creatorcontrib><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lok, Tsun Ming</au><au>Wang, Yang</au><au>Xu, Wendy Kaichun</au><au>Xie, Siwei</au><au>Ma, Hoi Tang</au><au>Poon, Randy Y. C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitotic slippage is determined by p31.sup.comet and the weakening of the spindle-assembly checkpoint</atitle><jtitle>Oncogene</jtitle><date>2020-03-26</date><risdate>2020</risdate><volume>39</volume><issue>13</issue><spage>2819</spage><pages>2819-</pages><issn>0950-9232</issn><abstract>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.</abstract><pub>Nature Publishing Group</pub><doi>10.1038/s41388-020-1187-6</doi></addata></record>
fulltext fulltext
identifier ISSN: 0950-9232
ispartof Oncogene, 2020-03, Vol.39 (13), p.2819
issn 0950-9232
language eng
recordid cdi_gale_infotracmisc_A618688990
source Alma/SFX Local Collection
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
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-09T11%3A48%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitotic%20slippage%20is%20determined%20by%20p31.sup.comet%20and%20the%20weakening%20of%20the%20spindle-assembly%20checkpoint&rft.jtitle=Oncogene&rft.au=Lok,%20Tsun%20Ming&rft.date=2020-03-26&rft.volume=39&rft.issue=13&rft.spage=2819&rft.pages=2819-&rft.issn=0950-9232&rft_id=info:doi/10.1038/s41388-020-1187-6&rft_dat=%3Cgale%3EA618688990%3C/gale%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_galeid=A618688990&rfr_iscdi=true