title: Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells.
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.
authors.affiliation: College of Life Sciences, West China Center of Medical Sciences, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dai
authors.forename: Tingjun
authors.initials: T
authors.lastname: Lei
authors.forename: Changhong
authors.initials: C
authors.lastname: Zhao
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Zhong
authors.forename: Yi-zhi
authors.initials: YZ
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Chenghua
authors.initials: C
authors.lastname: Li
authors.forename: Siyu
authors.initials: S
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Qintong
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D046912:Multiprotein Complexes / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016213:Cyclins; D046912:Multiprotein Complexes; D018844:Cyclin-Dependent Kinases