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.
A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis / M. Trinei, M. Giorgio, A. Cicalese, S. Barozzi, A. Ventura, E. Migliaccio, E. Milia, I. M. Padura, V. A. Raker, M. Maccarana, V. Petronilli, S. Minucci, P. Bernardi, L. Lanfrancone, P. G. Pelicci. - In: ONCOGENE. - ISSN 0950-9232. - 21:24(2002 May 30), pp. 3872-8-3878.
|Titolo:||A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis|
|Parole Chiave:||Animals; Antioxidants; Apoptosis; Tumor Suppressor Protein p53; DNA Damage; Deoxyguanosine; Mice, Knockout; Oxidation-Reduction; Shc Signaling Adaptor Proteins; Adaptor Proteins, Signal Transducing; Oxidative Stress; Signal Transduction; Cytochrome c Group; Mice; Reactive Oxygen Species; Protein Binding; Adaptor Proteins, Vesicular Transport; Transcriptional Activation; Gene Deletion; Oxygen; Polymerase Chain Reaction; Luciferases; Cells, Cultured; Proteins; Up-Regulation|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||30-mag-2002|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/sj.onc.1205513|
|Appare nelle tipologie:||01 - Articolo su periodico|