Department of Physiology, Faculty of Medicine, University of Valencia, Av. Blasco Ibáñez, 15 46010 Valencia, Spain.
Free Radic Res. 2011 Jun;45(6):643-52. doi: 10.3109/10715762.2011.571685. Epub 2011 Mar 31.
The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer. However, more recently it has been show that p53 is not only involved in cancer, but also in ageing. p53 is stimulated by stress, which in turn results in the activation of a wide range of transcriptional targets. Low-intensity stress will activate p53 in a manner which results in antioxidant response, thus protecting against ageing because of its antioxidant function. On the contrary, high-intensity activation of p53 will result in an increase of oxidative stress by activation of p53-mediated pro-oxidant targets, thus increasing the rate of ageing, but protecting against cancer.
p53 蛋白的经典功能与其在 DNA 损伤、细胞生长抑制、衰老和凋亡方面的作用有关。因此,它被称为“基因组的守护者”,并被认为是癌症发展过程中的最重要参与者之一。然而,最近的研究表明,p53 不仅与癌症有关,而且与衰老有关。p53 受到应激的刺激,应激反过来激活广泛的转录靶标。低强度的应激会以产生抗氧化反应的方式激活 p53,从而通过其抗氧化功能来保护机体免受衰老。相反,高强度的 p53 激活会通过激活 p53 介导的促氧化剂靶标增加氧化应激,从而增加衰老的速度,但能预防癌症。