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Publication : A nontranscriptional role for Oct4 in the regulation of mitotic entry.

First Author  Zhao R Year  2014
Journal  Proc Natl Acad Sci U S A Volume  111
Issue  44 Pages  15768-73
PubMed ID  25324523 Mgi Jnum  J:216673
Mgi Id  MGI:5609203 Doi  10.1073/pnas.1417518111
Citation  Zhao R, et al. (2014) A nontranscriptional role for Oct4 in the regulation of mitotic entry. Proc Natl Acad Sci U S A 111(44):15768-73
abstractText  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.
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