The "Two faces" of Tumor Suppressor p53-revisited.
The "Two faces" of Tumor Suppressor p53-revisited.
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发表时间：
2010
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通讯作者：
Martin L. Smith;M. S. Kumar
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作者：
Martin L. Smith;M. S. Kumar
大约15年前，包括我们在内的几个研究小组已经使用了携带野生型或突变型p53基因的配对细胞系来确定p53在细胞存活中的作用。这些是仅通过p53状态不同的同基因细胞系。当时的趋势是支持p53介导的凋亡。因此，p53-野生型细胞对DNA损伤敏感，而p53-突变型细胞被认为逃避凋亡。然而，这一发现并不普遍。特别是，在紫外线照射后，p53突变型细胞在几项研究中比其野生型p53对应物更敏感。发现p53控制一个主要的DNA修复途径，核苷酸切除修复（NER）修复紫外线损伤，为观察提供了一个机制。我们创造了“肿瘤抑制因子p53的两面”这一术语来说明p53一方面可以诱导凋亡，导致细胞敏感性，但p53也可以增强DNA修复速率，从而保护细胞免受DNA损伤。这一概念已被接受，并已扩展到其他DNA损伤剂。新的见解如何p53是“开关”从保护功能的凋亡功能进行审查。
About 15 years ago, several groups including ours had used matched pairs of cell lines carrying wild type or mutant p53 genes to ascertain a role for p53 in cell survival. These were isogenic cell lines differing only by p53 status. The trend at that time was to support p53-mediated apoptosis. Accordingly, p53-wildtype cells were sensitive to DNA damage compared to p53-mutant cells which were thought to evade apoptosis. However, this finding was not universal. In particular, after UV-radiation, p53-mutant cells were more sensitive than their wild type p53 counterparts in several studies. The finding that p53 controlled a major DNA repair pathway, nucleotide excision repair (NER) which repairs UV-damage, provided a mechanism for the observations. We coined the term "the two faces of tumor suppressor p53" to illustrate that p53 can on one hand induce apoptosis leading to cell sensitivity, but p53 can also enhance the rate of DNA repair thereby protecting cells from DNA damage. This concept has gained acceptance and has been expanded to other DNA-damaging agents. New insights into how p53 is "switched" from a protective function to an apoptotic function are reviewed.