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 language | English (US) |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Stem Cell Research |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - 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 ).
