ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4

被引：139

作者：

Kim, Myoung Ok ^{[1
]}

Kim, Sung-Hyun ^{[1
,2
]}

Cho, Yong-Yeon ^{[1
]}

Nadas, Janos ^{[1
]}

Jeong, Chul-Ho ^{[1
]}

Yao, Ke ^{[1
]}

Kim, Dong Joon ^{[1
]}

Yu, Dong-Hoon ^{[1
]}

Keum, Young-Sam ^{[1
]}

Lee, Kun-Yeong ^{[1
]}

Huang, Zunnan ^{[1
]}

Bode, Ann M. ^{[1
]}

Dong, Zigang ^{[1
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

[2] Kyungpook Natl Univ, Ctr Lab Anim Resources, Taegu, South Korea

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 03期

关键词：

DOCKING INTERACTIONS; MAP KINASES; DNA-BINDING; DIFFERENTIATION; MOUSE; OCT4; GENE; SOX2; CANCER; IDENTIFICATION;

D O I：

10.1038/nsmb.2217

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Understanding and controlling the mechanism by which stem cells balance self-renewal versus differentiation is of great importance for stem cell therapeutics. Klf4 promotes the self-renewal of embryonic stem cells, but the precise mechanism regulating this role of Klf4 is unclear. We found that ERK1 or ERK2 binds the activation domain of Klf4 and directly phosphorylates Klf4 at Ser123. This phosphorylation suppresses Klf4 activity, inducing embryonic stem cell differentiation. Conversely, inhibition of Klf4 phosphorylation enhances Klf4 activity and suppresses embryonic stem cell differentiation. Notably, phosphorylation of Klf4 by ERKs causes recruitment and binding of the F-box proteins beta TrCP1 or beta TrCP2 ( components of an ubiquitin E3 ligase) to the Klf4 N-terminal domain, which results in Klf4 ubiquitination and degradation. Overall, our data provide a molecular basis for the role of ERK1 and ERK2 in regulating Klf4-mediated mouse embryonic stem cell self-renewal.

引用

页码：283 / U38

页数：9

共 47 条

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