A nontranscriptional role for Oct4 in the regulation of mitotic entry

Rui Zhaoa, Richard W. Deibler, Paul H. Leroud, Andrea Ballabeni, Garrett C. Heffner, Patrick Cahan, Juli J. Unternaehrer, Marc W. Kirschner, George Q. Daley

Research output: Contribution to journalArticlepeer-review

Abstract

Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin-Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry.

Original languageEnglish (US)
Pages (from-to)15768-15773
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number44
DOIs
StatePublished - Nov 4 2014
Externally publishedYes

Keywords

  • CDC25
  • Cdk1
  • Mitotic entry
  • Oct4
  • Pluripotent stem cells

ASJC Scopus subject areas

  • General

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