Marcel Virginie, Nguyen Van Long Flora, Diaz Jean-Jacques
Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.
Cancers (Basel). 2018 May 21;10(5):152. doi: 10.3390/cancers10050152.
Since its discovery in 1979, p53 has shown multiple facets. Initially the tumor suppressor p53 protein was considered as a stress sensor able to maintain the genome integrity by regulating transcription of genes involved in cell cycle arrest, apoptosis and DNA repair. However, it rapidly came into light that p53 regulates gene expression to control a wider range of biological processes allowing rapid cell adaptation to environmental context. Among them, those related to cancer have been extensively documented. In addition to its role as transcription factor, scattered studies reported that p53 regulates miRNA processing, modulates protein activity by direct interaction or exhibits RNA-binding activity, thus suggesting a role of p53 in regulating several layers of gene expression not restricted to transcription. After 40 years of research, it appears more and more clearly that p53 is strongly implicated in translational regulation as well as in the control of the production and activity of the translational machinery. Translation control of specific mRNAs could provide yet unsuspected capabilities to this well-known guardian of the genome.
自1979年被发现以来,p53展现出了多个方面的特性。最初,肿瘤抑制蛋白p53被认为是一种应激传感器,能够通过调控参与细胞周期停滞、凋亡和DNA修复的基因转录来维持基因组完整性。然而,很快就发现p53通过调控基因表达来控制更广泛的生物学过程,使细胞能够快速适应环境。其中,与癌症相关的过程已有广泛记载。除了作为转录因子的作用外,零散的研究报告称p53还调控微小RNA(miRNA)加工,通过直接相互作用调节蛋白质活性或展现RNA结合活性,因此表明p53在调控不限于转录的多个基因表达层面发挥作用。经过40年的研究,越来越清楚地表明p53在翻译调控以及翻译机器的产生和活性控制中也发挥着重要作用。对特定信使核糖核酸(mRNA)的翻译控制可能为这位著名的基因组守护者提供尚未被认识到的能力。