Boehme Karen A, Blattner Christine
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Karlsruhe, Germany.
Crit Rev Biochem Mol Biol. 2009 Nov-Dec;44(6):367-92. doi: 10.3109/10409230903401507.
The p53 protein is one of the most important tumor suppressor proteins. Normally, the p53 protein is in a latent state. However, when its activity is required, e.g. upon DNA damage, nucleotide depletion or hypoxia, p53 becomes rapidly activated and initiates transcription of pro-apoptotic and cell cycle arrest-inducing target genes. The activity of p53 is regulated both by protein abundance and by post-translational modifications of pre-existing p53 molecules. In the 30 years of p53 research, a plethora of modifications and interaction partners that modulate p53's abundance and activity have been identified and new ones are continuously discovered. This review will summarize our current knowledge on the regulation of p53 abundance and activity.
p53蛋白是最重要的肿瘤抑制蛋白之一。正常情况下,p53蛋白处于潜伏状态。然而,当需要其活性时,例如在DNA损伤、核苷酸耗竭或缺氧时,p53会迅速被激活,并启动促凋亡和诱导细胞周期停滞的靶基因的转录。p53的活性既受蛋白质丰度的调节,也受现有p53分子的翻译后修饰的调节。在p53研究的30年里,已经鉴定出大量调节p53丰度和活性的修饰和相互作用伙伴,并且不断有新的被发现。本综述将总结我们目前关于p53丰度和活性调节的知识。