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J Biol Chem. 2012 Jul 20;287(30):25344-52. doi: 10.1074/jbc.M111.321760. Epub 2012 Apr 30.

Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells.

Author information

1
College of Life Sciences, West China Center of Medical Sciences, Sichuan University, Chengdu 610064, Sichuan, China.

Abstract

Protein phosphorylation plays an important role in the regulation of self-renewal and differentiation of embryonic stem cells. However, the responsible intracellular kinases are not well characterized. Here, we discovered that cyclin K protein was highly expressed in pluripotent embryonic stem cells but low in their differentiated derivatives or tissue-specific stem cells. Upon cell differentiation, the level of cyclin K protein was decreased. Furthermore, knockdown of cyclin K led to cell differentiation, which could be rescued by an expression construct resistant to RNA interference. Surprisingly, cyclin K did not interact with CDK9 protein in cells as thought previously. Instead, it associated with CrkRS (also known as CDK12) and CDC2L5 (also known as CDK13). Similar to cyclin K, both CDK12 and CDK13 proteins were highly expressed in murine embryonic stem cells and were decreased upon cell differentiation. Importantly, knockdown of either kinase resulted in differentiation. Thus, our studies have uncovered two novel protein kinase complexes that maintain self-renewal in embryonic stem cells.

PMID:
22547058
PMCID:
PMC3408147
DOI:
10.1074/jbc.M111.321760
[Indexed for MEDLINE]
Free PMC Article

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