ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal

Sung Hyun Kim, Myoung Ok Kim, Yong Yeon Cho, Ke Yao, Dong Joon Kim, Chul Ho Jeong, Dong Hoon Yu, Ki Beom Bae, Eun Jin Cho, Sung Keun Jung, Mee Hyun Lee, Hanyong Chen, Jae Young Kim, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Nanog regulates human and mouse embryonic stem (ES) cell self-renewal activity. Activation of ERKs signaling negatively regulates ES cell self-renewal and induces differentiation, but the mechanisms are not understood. We found that ERK1 binds and phosphorylates Nanog. Activation of MEK/ERKs signaling and phosphorylation of Nanog inhibit Nanog transactivation, inducing ES cell differentiation. Conversely, suppression of MEK/ERKs signaling enhances Nanog transactivation to inhibit ES cell differentiation. We observed that phosphorylation of Nanog by ERK1 decreases Nanog stability through ubiquitination-mediated protein degradation. Further, we found that this phosphorylation induces binding of FBXW8 with Nanog to reduce Nanog protein stability. Overall, our results demonstrated that ERKs-mediated Nanog phosphorylation plays an important role in self-renewal of ES cells through FBXW8-mediated Nanog protein stability.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalStem Cell Research
Volume13
Issue number1
DOIs
StatePublished - Jul 2014

Bibliographical note

Funding Information:
This work was supported by the Hormel Foundation and Cooperative Research Program for the Next-Generation BioGreen 21 Program (Project No. PJ009560 ).

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