Phosphorylation of Sox2 cooperates in reprogramming to pluripotent stem cells

Chul Ho Jeong, Yong Yeon Cho, Myoung Ok Kim, Sung Hyun Kim, Eun Jin Cho, Sung-Young Lee, Young J Jeon, Kun Y Lee, Ke Yao, Young Sam Keum, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by transduction of reprogramming factors, including Oct4, Sox2, Klf4, and c-Myc. A coordinated network of these factors was suggested to confer a pluripotency of iPSCs. Together with Oct4, Sox2 plays a major role as a master regulator in ESCs. However, the underlying mechanisms by which Sox2 contributes to self-renewal or reprogramming processes remain to be determined. Here, we provide new evidence for a phosphorylation-based regulation of Sox2 activity. Akt directly interacts with Sox2 and promotes its stabilization through phosphorylation at Thr118, which enhances the transcriptional activity of Sox2 in ESCs. Moreover, phosphorylation of Sox2 cooperates in the reprogramming of mouse embryonic fibroblasts by enabling more efficient induction of iPSCs. Overall, our studies provide new insights into the regulatory mechanism of Sox2 in ESCs and also provide a direct link between phosphorylation events and somatic cell reprogramming.

Original languageEnglish (US)
Pages (from-to)2141-2150
Number of pages10
JournalSTEM CELLS
Volume28
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Akt
  • Phosphorylation
  • Reprogramming
  • Self-renewal
  • Sox2

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