A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis
A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis
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DOI：
10.1038/sj.onc.1205513
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发表时间：
2002-05-30
期刊：
影响因子：
8
通讯作者：
Pelicci, PG
中科院分区：
文献类型：
--
作者：
Trinei, M;Giorgio, M;Pelicci, PG
相关证据将压力、氧化性细胞损伤的积累和低等生物和哺乳动物的衰老联系起来。我们在p66 Shc基因敲除小鼠中研究了它们之间的机制联系，这些小鼠的特点是对氧化应激的抵抗力增强，寿命延长。我们报告说，p66 Shc作为肿瘤抑制基因p53的下游靶点，并且对于应激激活的p53诱导细胞内氧化剂升高、细胞色素c释放和细胞凋亡的能力是必不可少的。p53的其他功能不受p66 Shc表达的影响。在基础条件下，p66 Shc-/-和p53 -/-细胞具有减少的细胞内氧化剂和氧化损伤的DNA的量。我们建议，稳态水平的细胞内氧化剂和氧化损伤的基因决定和调节的压力诱导的信号转导途径，涉及p53和p66 Shc。
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 hie 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.