Phosphorylation of Sox2 cooperates in reprogramming to pluripotent stem cells

Stem Cells. 2010 Dec;28(12):2141-50. doi: 10.1002/stem.540.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cellular Reprogramming* / drug effects
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / enzymology
  • Enzyme Activation / drug effects
  • Humans
  • Leukemia Inhibitory Factor / pharmacology
  • Mice
  • Molecular Sequence Data
  • Phosphorylation / drug effects
  • Phosphothreonine / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism*
  • Protein Binding / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Protein Stability / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • SOXB1 Transcription Factors / chemistry
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Transcription, Genetic / drug effects
  • Ubiquitin / metabolism

Substances

  • Leukemia Inhibitory Factor
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Ubiquitin
  • Phosphothreonine
  • Proto-Oncogene Proteins c-akt