Levine Arnold J, Oren Moshe
Arnold J. Levine is at the Institute for Advanced Study, School of Natural Sciences, Einstein Drive, Princeton, New Jersey 08540, USA.
Nat Rev Cancer. 2009 Oct;9(10):749-58. doi: 10.1038/nrc2723.
Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer. In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence. In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. The fourth decade of research may see new p53-based drugs to treat cancer. What is next is anybody's guess.
30年前,p53被发现是猿猴病毒40大T抗原(这种肿瘤病毒的癌蛋白)的细胞伴侣。p53研究的第一个十年见证了p53 DNA的克隆,以及人们认识到p53不是一个癌基因,而是一种在人类癌症中经常发生突变的肿瘤抑制因子。在研究的第二个十年,p53的功能被揭示出来:它是一种由应激诱导的转录因子,可促进细胞周期停滞、凋亡和衰老。在其被发现后的第三个十年,这种蛋白质的新功能被揭示出来,包括对胚胎植入所需的代谢途径和细胞因子的调节。研究的第四个十年可能会出现基于p53的新型抗癌药物。接下来会发生什么,谁也说不准。