Itch, an E3 ligase of Oct4, is required for embryonic stem cell self-renewal and pluripotency induction

J Cell Physiol. 2013 Jul;228(7):1443-51. doi: 10.1002/jcp.24297.

Abstract

Itch, a C2-WW-HECT domain ubiquitin E3 ligase, plays an important role in various biological processes. However, its role in embryonic stem cells (ESCs) remains unknown. Here, we report that Itch interacts with and targets pluripotency-associated transcription factor Oct4 for ubiquitination. Moreover, Itch enhances Oct4 transcriptional activities and controls Oct4 protein stability dependent on its catalytic activity. Importantly, silencing Itch expression compromises ESC self-renewal capacity and somatic cell reprogramming efficiency. Taken together, our study identifies Itch as a regulator of Oct4 stability and transcriptional activity, establishing a functional link between an E3 ligase and the regulation of pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Dedifferentiation
  • Cell Line
  • Cell Proliferation
  • Embryonal Carcinoma Stem Cells
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Protein Stability
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Pou5f1 protein, mouse
  • Repressor Proteins
  • ITCH protein, human
  • Itch protein, mouse
  • Ubiquitin-Protein Ligases