PKCδ-dependent deubiquitination and stabilization of Gadd45 in A431 cells overexposed to EGF

Chung Hang Leung, Wing Lam, Wei Jian Zhuang, Nai Sum Wang, David W F Fong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

15 Citations (Scopus)


Epidermal growth factor (EGF) receptor-overexpressing p53-deficient A431 cells response to toxic dose of EGF by G1 arrest and apoptosis was studied. We previously reported an increased expression of growth arrest and DNA-damage-inducible gene, Gadd45, in EGF-overexposed A431 cells. The mechanism for this induction was increased half-lives of mRNA and protein. In this study, using phorbol ester (a PKC activator) and specific inhibitors of PKC isoforms, we showed that protein kinase C-δ (PKCδ) was involved in the increase of Gadd45 protein stability. We further demonstrated that Gadd45 is ubiquitinated and is regulated by proteolysis. While EGF induced ubiquitination of total cellular proteins, there was a decrease in Gadd45 ubiquitination, which could be inhibited by Rottlerin, a PKCδ-specific inhibitor. These results suggest that an increase in Gadd45 stability may involve PKCδ-dependent ubiquitin - proteasome pathway.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2001

Scopus Subject Areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

User-Defined Keywords

  • A431 cell
  • Epidermal growth factor
  • Gadd45
  • Protein kinase C
  • Ubiquitination


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