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

2014; Elsevier BV; Volume: 13; Issue: 1 Linguagem: Inglês

10.1016/j.scr.2014.04.001

1876-7753

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,

3D Printing in Biomedical Research

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.