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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2006-1-27
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pubmed:abstractText |
The anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 controls progression to S phase and mitosis by stabilizing key APC/C ubiquitination substrates, including cyclin A. Examining Emi1 binding proteins, we identified the Evi5 oncogene as a regulator of Emi1 accumulation. Evi5 antagonizes SCF(betaTrCP)-dependent Emi1 ubiquitination and destruction by binding to a site adjacent to Emi1's DSGxxS degron and blocking both degron phosphorylation by Polo-like kinases and subsequent betaTrCP binding. Thus, Evi5 functions as a stabilizing factor maintaining Emi1 levels in S/G2 phase. Evi5 protein accumulates in early G1 following Plk1 destruction and is degraded in a Plk1- and ubiquitin-dependent manner in early mitosis. Ablation of Evi5 induces precocious degradation of Emi1 by the Plk/SCF(betaTrCP) pathway, causing premature APC/C activation; cyclin destruction; cell-cycle arrest; centrosome overduplication; and, finally, mitotic catastrophe. We propose that the balance of Evi5 and Polo-like kinase activities determines the timely accumulation of Emi1 and cyclin, ensuring mitotic fidelity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin A,
http://linkedlifedata.com/resource/pubmed/chemical/EVI5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/F-Box Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FBXO5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligase Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/anaphase-promoting complex,
http://linkedlifedata.com/resource/pubmed/chemical/polo-like kinase 1
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
124
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
367-80
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:16439210-Anaphase,
pubmed-meshheading:16439210-Animals,
pubmed-meshheading:16439210-Cell Cycle,
pubmed-meshheading:16439210-Cell Cycle Proteins,
pubmed-meshheading:16439210-Cell Line,
pubmed-meshheading:16439210-Cyclin A,
pubmed-meshheading:16439210-F-Box Proteins,
pubmed-meshheading:16439210-HeLa Cells,
pubmed-meshheading:16439210-Humans,
pubmed-meshheading:16439210-Interphase,
pubmed-meshheading:16439210-Models, Biological,
pubmed-meshheading:16439210-Nuclear Proteins,
pubmed-meshheading:16439210-Phosphorylation,
pubmed-meshheading:16439210-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16439210-Proto-Oncogene Proteins,
pubmed-meshheading:16439210-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:16439210-Two-Hybrid System Techniques,
pubmed-meshheading:16439210-Ubiquitin-Protein Ligase Complexes,
pubmed-meshheading:16439210-Xenopus
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pubmed:year |
2006
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pubmed:articleTitle |
The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1.
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pubmed:affiliation |
Department of Cancer Biology, Stanford University School of Medicine, CA 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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