A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis

Mirella Trinei, Marco Giorgio, Angelo Cicalese, Sara Barozzi, Andrea Ventura, Enrica Migliaccio, Elisabetta Milia, Ines Martin Padura, Veronica A. Raker, Marco Maccarana, Valeria Petronilli, Saverio Minucci, Paolo Bernardi, Luisa Lanfrancone, Pier Giuseppe Pelicci

Research output: Contribution to journalArticlepeer-review

Abstract

Correlative evidence links stress, accumulation of oxidative cellular damage and ageing in lower organisms and in mammals. We investigated their mechanistic connections in p66Shc knockout mice, which are characterized by increased resistance to oxidative stress and extended life span. We report that p66Shc acts as a downstream target of the tumour suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. Other functions of p53 are not influenced by p66Shc expression. In basal conditions, p66Shc-/- and p53-/- cells have reduced amounts of intracellular oxidants and oxidation-damaged DNA. We propose that steady-state levels of intracellular oxidants and oxidative damage are genetically determined and regulated by a stress-induced signal transduction pathway involving p53 and p66Shc.

Original languageEnglish
Pages (from-to)3872-3878
Number of pages7
JournalOncogene
Volume21
Issue number24
DOIs
Publication statusPublished - May 30 2002

Keywords

  • Ageing
  • Apoptosis
  • Oxidative stress
  • p53
  • Shc

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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