DNA damage down-regulates ΔNp63α and induces apoptosis independent of wild type p53

Biochem Biophys Res Commun. 2012 Jun 29;423(2):338-43. doi: 10.1016/j.bbrc.2012.05.126. Epub 2012 May 31.

Abstract

The tumor suppressor p53 is pivotal in cell growth arrest and apoptosis upon cellular stresses including DNA damage. Mounting evidence indicates that p63 proteins, which are homologs of p53, are also involved in apoptosis under certain circumstances. In this study, we found that treatment with DNA damage agents leads to down-regulation of ΔNp63α and induces apoptosis in FaDu and HaCat cells carrying mutant p53. Further study shows that DNA damage reduces steady-state mRNA level of ΔNp63α, but has little effect on its protein stability. In addition, knockdown of endogenous ΔNp63α directly induces apoptosis and sensitizes cells to DNA damage, while exogenous expression of ΔNp63α partially confers cellular resistance to DNA damage. Together, these data suggest that DNA damage down-regulates ΔNp63α, which may directly contribute to DNA damage-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Line
  • Cell Survival
  • DNA Damage*
  • Down-Regulation
  • Humans
  • Mutation
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins