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

Hui Ming Xu1, Bing Liao, Qian Jun Zhang

  • 1Developmental Biology Department, Health Science Center, Shanghai Second Medical University and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 411 He Fei Road, Shanghai 200025, China.

The Journal of Biological Chemistry
|March 30, 2004
PubMed

Insights

A novel ubiquitin ligase, Wwp2, targets Oct-4 for degradation, impacting embryonic stem cell fate. This ubiquitination suppresses Oct-4

Area of Science:

  • Stem cell biology
  • Molecular and cellular biology
  • Ubiquitin-proteasome system

Background:

  • Oct-4 is a critical POU transcription factor regulating embryonic stem cell pluripotency.
  • Mechanisms controlling Oct-4 activation and expression are not fully understood.

Purpose of the Study:

  • To identify novel regulators of Oct-4.
  • To investigate the post-translational modification of Oct-4.

Main Methods:

  • Identified and characterized a novel murine ubiquitin ligase, Wwp2.
  • Assessed Wwp2's interaction with Oct-4 using in vivo and in vitro assays.
  • Analyzed Oct-4 ubiquitination, degradation, and transcriptional activity under Wwp2 modulation and proteasome inhibition.

Main Results:

  • Wwp2 specifically interacts with Oct-4 and promotes its ubiquitination.
  • Catalytically inactive Wwp2 mutant prevents Oct-4 ubiquitination.
  • Wwp2 induces Oct-4 degradation via the proteasome pathway.
  • Ubiquitination of Oct-4 suppresses its transcriptional activity.
  • Wwp2 overexpression reduces Oct-4 transcriptional activity in embryonic stem cells.

Conclusions:

  • Oct-4 undergoes post-translational modification by ubiquitination.
  • Ubiquitination significantly suppresses Oct-4's transcriptional activity.
  • Wwp2-mediated ubiquitination is a key regulatory mechanism for Oct-4 function.
  • Oct-4's functional status, not just expression level, dictates its activity in stem cell fate determination.

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