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Cyclin E overexpression impairs progression through mitosis by inhibiting APC(Cdh1)

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Overview

related to degree

  • Keck, Jamie, Ph.D. in Biology, Scripps Research 1999 - 2006

authors

  • Keck, Jamie
  • Summers, M. K.
  • Tedesco, D.
  • Ekholm-Reed, S.
  • Chuang, L. C.
  • Jackson, P. K.
  • Reed, Steven

publication date

  • July 2007

journal

  • Journal of Cell Biology  Journal

abstract

  • 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 (APC(Cdh1)) activity that persists as cells progress up to and through the early stages of mitosis, resulting in the abnormal accumulation of APC(Cdh1) 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.

subject areas

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cell Cycle
  • Cell Line
  • Cyclin A
  • Cyclin B
  • Cyclin B1
  • Cyclin E
  • Cyclin-Dependent Kinase 2
  • Humans
  • Microscopy, Fluorescence
  • Mitosis
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Securin
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases
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Identity

PubMed Central ID

  • PMC2064850

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200703202

PubMed ID

  • 17664332
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Additional Document Info

start page

  • 371

end page

  • 385

volume

  • 178

issue

  • 3

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