Pluripotent cell division cycles are driven by ectopic Cdk2, cyclin A/E and E2F activities

Elaine Stead, Josephine White, Renate Faast, Simon Conn, Sherilyn Goldstone, Joy Rathjen, Urvashi Dhingra, Peter Rathjen, Duncan Walker, Stephen Dalton

Research output: Contribution to journalArticle

286 Citations (Scopus)

Abstract

Pluripotent cells of embryonic origin proliferate at unusually rapid rates and have a characteristic cell cycle structure with truncated gap phases. To define the molecular basis for this we have characterized the cell cycle control of murine embryonic stem cells and early primitive ectoderm-like cells. These cells display precocious Cdk2, cyclin A and cyclin E kinase activities that are conspicuously cell cycle independent. Suppression of Cdk2 activity significantly decreased cycling times of pluripotent cells, indicating it to be rate-limiting for rapid cell division, although this had no impact on cell cycle structure and the establishment of extended gap phases. Cdc2-cyclin B was the only Cdk activity that was identified to be cell cycle regulated in pluripotent cells. Cell cycle regulation of cyclin B levels and y15 regulation of Cdc2 contribute to the temporal changes in Cdc2-cyclin B activity. E2F target genes are constitutively active throughout the cell cycle, reflecting the low activity of pocket proteins such as p107 and pRb and constitutive activity of pRb-kinases. These results show that rapid cell division cycles in primitive cells of embryonic origin are driven by extreme levels of Cdk activity that lack normal cell cycle periodicity.

Original languageEnglish
Pages (from-to)8320-8333
Number of pages14
JournalOncogene
Volume21
Issue number54
DOIs
Publication statusPublished - 25 Nov 2002
Externally publishedYes

Keywords

  • Cell cycle
  • Pluripotent
  • Stem cell

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    Stead, E., White, J., Faast, R., Conn, S., Goldstone, S., Rathjen, J., Dhingra, U., Rathjen, P., Walker, D., & Dalton, S. (2002). Pluripotent cell division cycles are driven by ectopic Cdk2, cyclin A/E and E2F activities. Oncogene, 21(54), 8320-8333. https://doi.org/10.1038/sj.onc.1206015