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U-box-type ubiquitin E4 ligase, UFD2a attenuates cisplatin mediated degradation of DeltaNp63alpha

Aditi Chatterjee1, Sunil Upadhyay, Xiaofei Chang

  • 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.

Cell Cycle (Georgetown, Tex.)
|April 18, 2008
PubMed

Insights

The E4 ubiquitin ligase UFD2a stabilizes DeltaNp63alpha, a key survival factor in head and neck cancer. UFD2a regulates DeltaNp63alpha levels and activity, impacting cisplatin-induced cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • DeltaNp63alpha is a critical survival factor in head and neck squamous cell carcinoma.
  • DeltaNp63alpha is downregulated by DNA damaging agents like cisplatin.
  • The post-translational regulation of DeltaNp63alpha stability is poorly understood.

Purpose of the Study:

  • To investigate the interaction between DeltaNp63alpha and UFD2a.
  • To elucidate the role of UFD2a in DeltaNp63alpha protein stability and function.
  • To understand the regulation of DeltaNp63alpha in response to cisplatin treatment.

Main Methods:

  • Co-immunoprecipitation to detect protein interactions.
  • Western blotting to assess protein levels and ubiquitylation.
  • RNA interference (RNAi) to downregulate UFD2a expression.
  • Reporter assays to measure transcriptional activity.

Main Results:

  • DeltaNp63alpha physically interacts with UFD2a, a U-box-type E4 ubiquitin ligase.
  • UFD2a stabilizes DeltaNp63alpha and attenuates its ubiquitylation, even with cisplatin.
  • Ectopic UFD2a expression enhances DeltaNp63alpha's half-life and transcriptional repression.
  • RNAi-mediated downregulation of UFD2a leads to DeltaNp63alpha degradation.

Conclusions:

  • UFD2a stabilizes DeltaNp63alpha protein levels.
  • UFD2a plays a significant role in regulating DeltaNp63alpha stability and activity.
  • UFD2a may be crucial in mediating p63-dependent cell death in response to cisplatin.

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