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Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss

Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which un...

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Autores principales: Weaver, Beth A.A., Bonday, Zahid Q., Putkey, Frances R., Kops, Geert J.P.L., Silk, Alain D., Cleveland, Don W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173788/
https://www.ncbi.nlm.nih.gov/pubmed/12925705
http://dx.doi.org/10.1083/jcb.200303167
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author Weaver, Beth A.A.
Bonday, Zahid Q.
Putkey, Frances R.
Kops, Geert J.P.L.
Silk, Alain D.
Cleveland, Don W.
author_facet Weaver, Beth A.A.
Bonday, Zahid Q.
Putkey, Frances R.
Kops, Geert J.P.L.
Silk, Alain D.
Cleveland, Don W.
author_sort Weaver, Beth A.A.
collection PubMed
description Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. Here, we show that single unattached kinetochores depleted of CENP-E cannot block entry into anaphase, resulting in aneuploidy in 25% of divisions in primary mouse fibroblasts in vitro and in 95% of regenerating hepatocytes in vivo. Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. CENP-E binds to and directly stimulates the kinase activity of purified BubR1 in vitro. Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal.
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spelling pubmed-21737882008-05-01 Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss Weaver, Beth A.A. Bonday, Zahid Q. Putkey, Frances R. Kops, Geert J.P.L. Silk, Alain D. Cleveland, Don W. J Cell Biol Article Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. Here, we show that single unattached kinetochores depleted of CENP-E cannot block entry into anaphase, resulting in aneuploidy in 25% of divisions in primary mouse fibroblasts in vitro and in 95% of regenerating hepatocytes in vivo. Without CENP-E, diminished levels of BubR1 are recruited to kinetochores and BubR1 kinase activity remains at basal levels. CENP-E binds to and directly stimulates the kinase activity of purified BubR1 in vitro. Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. The Rockefeller University Press 2003-08-18 /pmc/articles/PMC2173788/ /pubmed/12925705 http://dx.doi.org/10.1083/jcb.200303167 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Weaver, Beth A.A.
Bonday, Zahid Q.
Putkey, Frances R.
Kops, Geert J.P.L.
Silk, Alain D.
Cleveland, Don W.
Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
title Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
title_full Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
title_fullStr Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
title_full_unstemmed Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
title_short Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
title_sort centromere-associated protein-e is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173788/
https://www.ncbi.nlm.nih.gov/pubmed/12925705
http://dx.doi.org/10.1083/jcb.200303167
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