Wwp2, An E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination

Hui Ming Xu, Bing Liao, Qian Jun Zhang, Bei Bei Wang, Hui Li, Xiao Min Zhong, Hui Zhen Sheng, Ying Xin Zhao, Ying Ming Zhao, Ying Jin

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

The POU transcription factor Oct-4 is a master regulator affecting the fate of pluripotent embryonic stem cells. However, the precise mechanisms by which the activation and expression of Oct-4 are regulated still remain to be elucidated. We describe here a novel murine ubiquitin ligase, Wwp2, that specifically interacts with Oct-4 and promotes its ubiquitination both in vivo and in vitro. Remarkably, the expression of a catalytically inactive point mutant of Wwp2 abolishes Oct-4 ubiquitination. Moreover, Wwp2 promotes Oct-4 degradation in the presence of overexpressed ubiquitin. The degradation is blocked by treatment with proteasome inhibitor. Fusion of a single ubiquitin to Oct-4 inactivates its transcriptional activity in a heterologous Oct-4-driven reporter system. Furthermore, overexpression of Wwp2 in embryonic stem cells significantly reduces the Oct-4-transcriptional activities. Collectively, we demonstrate for the first time that Oct-4 can be post-translationally modified by ubiquitination and that this modification dramatically suppresses its transcriptional activity. These results reveal that the functional status of Oct-4, in addition to its expression level, dictates its transcriptional activity, and the results open up a new avenue to understand how Oct-4 defines the fate of embryonic stem cells.

Original languageEnglish (US)
Pages (from-to)23495-23503
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number22
DOIs
StatePublished - May 28 2004
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Xu, H. M., Liao, B., Zhang, Q. J., Wang, B. B., Li, H., Zhong, X. M., Sheng, H. Z., Zhao, Y. X., Zhao, Y. M., & Jin, Y. (2004). Wwp2, An E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. Journal of Biological Chemistry, 279(22), 23495-23503. https://doi.org/10.1074/jbc.M400516200