| Literature DB >> 24793005 |
Sung-Hyun Kim1, Myoung Ok Kim1, Yong-Yeon Cho2, Ke Yao2, Dong Joon Kim2, Chul-Ho Jeong2, Dong Hoon Yu2, Ki Beom Bae2, Eun Jin Cho2, Sung Keun Jung2, Mee Hyun Lee2, Hanyong Chen2, Jae Young Kim3, Ann M Bode2, Zigang Dong4.
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.Entities:
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Year: 2014 PMID： 24793005 DOI： 10.1016/j.scr.2014.04.001
Source DB: PubMed Journal: Stem Cell Res ISSN： 1873-5061 Impact factor: 2.020