p73beta, unlike p53, suppresses growth and induces apoptosis of human papillomavirus E6-expressing cancer cells

Int J Oncol. 1998 Jul;13(1):5-9. doi: 10.3892/ijo.13.1.5.

Abstract

Human papillomavirus (HPV) is the major cause of cervical cancer worldwide. HPV-E6 protein targets the p53 tumor suppressor protein for degradation by ubiquitin-mediated proteolysis making such cancers resistant to p53-gene therapy. Here we show that infection of human cancer cells by E6-expressing adenovirus (Ad-E6) leads to degradation of both wild-type or mutant p53 protein. Interestingly, the p53-homologue candidate tumor suppressor p73 is not degraded in Ad-E6 infected cancer cells. Wild-type p73beta and not wild-type p53 or mutant p73 is a potent inhibitor of cancer colony growth and inducer of apoptosis, despite HPV-E6 overexpression. The results suggest a novel strategy using p73beta in gene therapy of HPV-E6 expressing cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • DNA-Binding Proteins / physiology*
  • Genes, Tumor Suppressor*
  • Humans
  • Ligases / metabolism
  • Nuclear Proteins / physiology*
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology*
  • Protein Binding
  • Repressor Proteins*
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / physiology*
  • Tumor Suppressor Proteins
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology*
  • Ubiquitin-Protein Ligases

Substances

  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • p73 protein, human
  • Ubiquitin-Protein Ligases
  • Ligases