p53 Laboratory (A*STAR), 8A Biomedical Grove, Immunos, Singapore.
Cell Cycle. 2010 Feb 1;9(3):540-7. doi: 10.4161/cc.9.3.10516.
The p53 protein is the most commonly mutated tumor suppressor gene in man. Understanding of its evolutionary origins have been enhanced by the recent discovery of p53 family genes in the Sea Anemone Nematostella vectensis. This amino acid sequence conservation has been reflected in biological activity since the early p53 proteins, like their human counterparts, are responsible for DNA damage-induced cellular apoptosis, albeit restricted to the germ cell compartment in model organisms such as the nematode and fruit fly. In vertebrates from zebrafish to man the function of p53 is tightly and absolutely constrained by a negative regulator Mdm2. However the Mdm2 gene has not been detected in the genome of the model nematode (C. elegans) and insect (D. melanogaster) species. We have found that the p53 gene and the Mdm2 gene are present in Placozoans, one of the simplest of all free living multi-cellular organisms, implying that both proteins arose much earlier in evolution than previously thought. Detailed sequence analysis shows the exceptional retention of key features of both proteins from man to Placazoan implying that the p53-Mdm2 interaction and its regulation have been conserved from a basal eumetazoan since the pre-cambrian era over 1 billion years ago.
p53 蛋白是人类最常见的突变型肿瘤抑制基因。最近在海葵 Nematostella vectensis 中发现了 p53 家族基因，这增强了人们对其进化起源的理解。这种氨基酸序列的保守性反映在生物学活性中，因为早期的 p53 蛋白，就像它们的人类对应物一样，负责 DNA 损伤诱导的细胞凋亡，尽管这种作用仅限于线虫和果蝇等模式生物的生殖细胞区室。在从斑马鱼到人类的脊椎动物中，p53 的功能受到负调节因子 Mdm2 的严格和绝对限制。然而，Mdm2 基因并未在模式线虫（秀丽隐杆线虫）和昆虫（黑腹果蝇）物种的基因组中检测到。我们发现，p53 基因和 Mdm2 基因存在于最简单的多细胞生物之一——扁盘动物中，这表明这两种蛋白的出现比之前认为的要早得多。详细的序列分析表明，从人类到扁盘动物，这两种蛋白的关键特征都得到了异常保留，这意味着 p53-Mdm2 相互作用及其调节自前寒武纪以来就已经从基础后生动物中保守下来，距今已有 10 多亿年的历史。
