Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1

Jamie M. Keck, Matthew K. Summers, Donato Tedesco, Susanna Ekholm-Reed, Li Chiou Chuang, Peter K. Jackson, Steven I. Reed

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Overexpression of cyclin E, an activator of cyclindependent 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.

Original languageEnglish (US)
Pages (from-to)371-385
Number of pages15
JournalJournal of Cell Biology
Volume178
Issue number3
DOIs
StatePublished - Jul 30 2007
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'Cyclin E overexpression impairs progression through mitosis by inhibiting APC<sup>Cdh1</sup>'. Together they form a unique fingerprint.

Cite this