Related Experiment Video
Updated: Apr 30, 2026

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal
Sung-Hyun Kim1, Myoung Ok Kim1, Yong-Yeon Cho2
1The Hormel Institute, University of Minnesota, 801, 16th AVE, NE, Austin, MN 55912, USA; Kyungpook National University, Center for Laboratory Animal Resources, School of Animal BT Science, Department of Biochemistry, School of Dentistry, Dae-gu, Republic of Korea.
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.
Related Concept Videos
Maintenance of the ES Cell State
Somatic to iPS Cell Reprogramming
PI3K/mTOR/AKT Signaling Pathway
Negative Regulator Molecules
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Methods of Nuclear Reprogramming

