Serine 347 Phosphorylation by JNKs Negatively Regulates OCT4 Protein Stability in Mouse Embryonic Stem Cells

Ki Beom Bae, Dong Hoon Yu, Kun Yeong Lee, Ke Yao, Joohyun Ryu, Do Young Lim, Tatyana A. Zykova, Myoung Ok Kim, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The POU transcription factor OCT4 is critical for maintaining the undifferentiated state of embryonic stem cells (ESCs) and generating induced pluripotent stem cells (iPSCs), but its precise mechanisms of action remain poorly understood. Here, we investigated the role of OCT4 phosphorylation in the biological functions of ESCs. We observed that c-Jun N-terminal kinases (JNKs) directly interacted with and phosphorylated OCT4 at serine 347, which inhibited the transcriptional activity of OCT4. Moreover, phosphorylation of OCT4 induced binding of FBXW8, which reduced OCT4 protein stability and enhanced its proteasomal degradation. We also found that the mutant OCT4 (S347A) might delay the differentiation process of mouse ESCs and enhance the efficiency of generating iPSCs. These results demonstrated that OCT4 phosphorylation on serine 347 by JNKs plays an important role in its stability, transcriptional activities, and self-renewal of mouse ESCs. In this article, Bae and colleagues show that JNKs directly interact with and phosphorylate OCT4 at serine 347. This phosphorylation inhibits the transcriptional activity and stability of OCT4 in mouse ESCs. The mutant OCT4 (S347A) might delay the differentiation process of mouse ESCs and enhance the efficiency of generating iPSCs.

Original languageEnglish (US)
Pages (from-to)2050-2064
Number of pages15
JournalStem Cell Reports
Volume9
Issue number6
DOIs
StatePublished - Dec 12 2017

Bibliographical note

Funding Information:
We would like to thank Dr. Tia Rai and Nicki Brickman-Van Erkel for critical reading and assisting with the manuscript submission. This work was supported by The Hormel Foundation .

Publisher Copyright:
© 2017 The Authors

Keywords

  • FBXW8
  • JNK
  • OCT4
  • embryonic stem cells
  • induced pluripotent stem cells
  • phosphorylation
  • self-renewal
  • ubiquitination

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