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Updated: Jul 7, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or apoptin

Poramaporn Klanrit1, Marcella B Flinterman, Edward W Odell

  • 1Head and Neck Oncology Group, King's College London Dental Institute, London, United Kingdom.

Cell Cycle (Georgetown, Tex.)
|February 8, 2008
PubMed

Insights

Viral proteins E1A and Apoptin induce tumor cell death by activating the p73 protein pathway, independent of p53 function. This highlights p73

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Virology

Background:

  • The p53 protein family, including p73, plays a critical role in regulating cell cycle and apoptosis.
  • Previous studies demonstrated p53-independent, tumor-specific cell death induced by viral proteins E1A and Apoptin.

Purpose of the Study:

  • To investigate the role of p73 in viral protein-induced apoptosis.
  • To elucidate the mechanism by which E1A and Apoptin induce cancer cell death in a p53-deficient context.

Main Methods:

  • Analysis of endogenous TAp73 and PUMA expression following E1A and Apoptin treatment.
  • Overexpression of TAp73 isoforms and DeltaNp73alpha to assess their effect on viral protein-induced apoptosis.
  • Gene knockout of c-Abl to evaluate its role in E1A-induced apoptosis.
  • In vitro and in vivo experiments using p53-deficient cancer cells and HNSCC xenografts.
  • Doxycycline-inducible system to study p73 isoform selectivity and stability.

Main Results:

  • E1A and Apoptin induced endogenous TAp73 and PUMA expression independently of p53.
  • Overexpression of TAp73, particularly TAp73beta, sensitized cells to E1A and Apoptin, while DeltaNp73alpha inhibited this effect.
  • Knockout of c-Abl attenuated E1A-induced apoptosis.
  • TAp73beta overexpression induced apoptosis in p53-deficient cancer cells and HNSCC xenografts.
  • Specific p73 isoforms exhibited target selectivity and differential protein stability.

Conclusions:

  • Viral proteins E1A and Apoptin induce apoptosis by activating the TAp73 pathway in a p53-independent manner.
  • TAp73 isoforms play a crucial and diverse role in mediating tumor cell death in response to viral oncoproteins.
  • Targeting the p73 pathway represents a potential therapeutic strategy for cancers lacking p53 function.

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