Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1

Overexpression of cyclin E, an activator of cyclin-dependent kinase 2, has been linked to human cancer. In cell culture models, the forced expression of cyclin E leads to aneuploidy and polyploidy, which is consistent with a direct role of cyclin E overexpression in tumorigenesis. In this study, we...

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Main Authors:	Keck, Jamie M., Summers, Matthew K., Tedesco, Donato, Ekholm-Reed, Susanna, Chuang, Li-Chiou, Jackson, Peter K., Reed, Steven I.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064850/

id	pubmed-2064850
recordtype	oai_dc
spelling	pubmed-20648502008-01-30 Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1 Keck, Jamie M. Summers, Matthew K. Tedesco, Donato Ekholm-Reed, Susanna Chuang, Li-Chiou Jackson, Peter K. Reed, Steven I. Research Articles Overexpression of cyclin E, an activator of cyclin-dependent kinase 2, has been linked to human cancer. In cell culture models, the forced expression of cyclin E leads to aneuploidy and polyploidy, which is consistent with a direct role of cyclin E overexpression in tumorigenesis. In this study, we show that the overexpression of cyclin E has a direct effect on progression through the latter stages of mitotic prometaphase before the complete alignment of chromosomes at the metaphase plate. In some cases, such cells fail to divide chromosomes, resulting in polyploidy. In others, cells proceed to anaphase without the complete alignment of chromosomes. These phenotypes can be explained by an ability of overexpressed cyclin E to inhibit residual anaphase-promoting complex (APCCdh1) activity that persists as cells progress up to and through the early stages of mitosis, resulting in the abnormal accumulation of APCCdh1 substrates as cells enter mitosis. We further show that the accumulation of securin and cyclin B1 can account for the cyclin E–mediated mitotic phenotype. The Rockefeller University Press 2007-07-30 /pmc/articles/PMC2064850/ /pubmed/17664332 http://dx.doi.org/10.1083/jcb.200703202 Text en Copyright © 2007, 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/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Keck, Jamie M. Summers, Matthew K. Tedesco, Donato Ekholm-Reed, Susanna Chuang, Li-Chiou Jackson, Peter K. Reed, Steven I.
spellingShingle	Keck, Jamie M. Summers, Matthew K. Tedesco, Donato Ekholm-Reed, Susanna Chuang, Li-Chiou Jackson, Peter K. Reed, Steven I. Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1
author_facet	Keck, Jamie M. Summers, Matthew K. Tedesco, Donato Ekholm-Reed, Susanna Chuang, Li-Chiou Jackson, Peter K. Reed, Steven I.
author_sort	Keck, Jamie M.
title	Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1
title_short	Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1
title_full	Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1
title_fullStr	Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1
title_full_unstemmed	Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1
title_sort	cyclin e overexpression impairs progression through mitosis by inhibiting apccdh1
description	Overexpression of cyclin E, an activator of cyclin-dependent kinase 2, has been linked to human cancer. In cell culture models, the forced expression of cyclin E leads to aneuploidy and polyploidy, which is consistent with a direct role of cyclin E overexpression in tumorigenesis. In this study, we show that the overexpression of cyclin E has a direct effect on progression through the latter stages of mitotic prometaphase before the complete alignment of chromosomes at the metaphase plate. In some cases, such cells fail to divide chromosomes, resulting in polyploidy. In others, cells proceed to anaphase without the complete alignment of chromosomes. These phenotypes can be explained by an ability of overexpressed cyclin E to inhibit residual anaphase-promoting complex (APCCdh1) activity that persists as cells progress up to and through the early stages of mitosis, resulting in the abnormal accumulation of APCCdh1 substrates as cells enter mitosis. We further show that the accumulation of securin and cyclin B1 can account for the cyclin E–mediated mitotic phenotype.
publisher	The Rockefeller University Press
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064850/
_version_	1611406876221636608

Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1

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