Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 강동민 | - |
dc.date.accessioned | 2016-08-28T12:08:11Z | - |
dc.date.available | 2016-08-28T12:08:11Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.other | OAK-7924 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/221914 | - |
dc.description.abstract | The E3 ubiquitin-protein ligase Chfr is a mitotic stress checkpoint protein that delays mitotic entry in response to microtubule damage; however, the molecular mechanism by which Chfr accomplishes this remains elusive. Here, we show that Chfr levels are elevated in response to microtubule-damaging stress. Moreover, G 2/M transition is associated with cell cycle-dependent turnover of Chfr accompanied by high autoubiquitylation activity, suggesting that regulation of Chfr levels and auto-ubiquitylation activity are functionally significant. To test this, we generated Chfr mutants Chfr-K2A and Chfr-K5A in which putative lysine target sites of auto-ubiquitylation were replaced with alanine. Chfr-K2A did not undergo cell cycle-dependent degradation, and its levels remained high during G 2/M phase. The elevated levels of Chfr-K2A caused a significant reduction in phosphohistone H3 levels and cyclinB1/Cdk1 kinase activities, leading to mitotic entry delay. Notably, polo-like kinase 1 levels at G 2 phase, but not at S phase, were ∼2-3-fold lower in cells expressing Chfr-K2A than in wild-type Chfr-expressing cells. Consistent with this, ubiquitylation of Plk1 at G 2 phase was accelerated in Chfr-K2A-expressing cells. In contrast, Aurora A levels remained constant, indicating that Plk1 is a major target of Chfr in controlling the timing of mitotic entry. Indeed, overexpression of Plk1 in Chfr-K2A-expressing cells restored cyclin B1/Cdk1 kinase activity and promoted mitotic entry. Collectively, these data indicate that Chfr auto-ubiquitylation is required to allow Plk1 to accumulate to levels necessary for activation of cyclin B1/Cdk1 kinase and mitotic entry. Our results provide the first evidence that Chfr auto-ubiquitylation and degradation are important for the G 2/M transition. | - |
dc.language | English | - |
dc.title | The auto-ubiquitylation of E3 ubiquitin-protein ligase Chfr at G 2 phase is required for accumulation of polo-like kinase 1 and mitotic entry in mammalian cells | - |
dc.type | Article | - |
dc.relation.issue | 35 | - |
dc.relation.volume | 286 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 30615 | - |
dc.relation.lastpage | 30623 | - |
dc.relation.journaltitle | Journal of Biological Chemistry | - |
dc.identifier.doi | 10.1074/jbc.M111.231803 | - |
dc.identifier.wosid | WOS:000294283600041 | - |
dc.identifier.scopusid | 2-s2.0-80052196035 | - |
dc.author.google | Kim J.-S. | - |
dc.author.google | Park Y.-Y. | - |
dc.author.google | Park S.-Y. | - |
dc.author.google | Cho H. | - |
dc.author.google | Kang D. | - |
dc.contributor.scopusid | 강동민(13103841000) | - |
dc.date.modifydate | 20230210131016 | - |