期刊
STEM CELL RESEARCH
卷 13, 期 1, 页码 1-11出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2014.04.001
关键词
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资金
- Hormel Foundation
- Cooperative Research Program for the Next-Generation BioGreen 21 Program [PJ009560]
- National Research Foundation of Korea [21A20132212438] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Rural Development Administration (RDA), Republic of Korea [PJ009560012014] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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. (C) 2014 The Authors. Published by Elsevier B.V.
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