Capuozzo Maurizio, Santorsola Mariachiara, Bocchetti Marco, Perri Francesco, Cascella Marco, Granata Vincenza, Celotto Venere, Gualillo Oreste, Cossu Alessia Maria, Nasti Guglielmo, Caraglia Michele, Ottaiano Alessandro
Coordinamento Farmaceutico, ASL-Naples-3, 80056 Ercolano, Italy.
Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Via M. Semmola, 80131 Naples, Italy.
Biology (Basel). 2022 Sep 6;11(9):1325. doi: 10.3390/biology11091325.
p53 tumour suppressor gene is our major barrier against neoplastic transformation. It is involved in many cellular functions, including cell cycle arrest, senescence, DNA repair, apoptosis, autophagy, cell metabolism, ferroptosis, immune system regulation, generation of reactive oxygen species, mitochondrial function, global regulation of gene expression, miRNAs, etc. Its crucial importance is denounced by the high percentage of amino acid sequence identity between very different species (Homo sapiens, Drosophila melanogaster, Rattus norvegicus, Danio rerio, Canis lupus familiaris, Gekko japonicus). Many of its activities allowed life on Earth (e.g., repair from radiation-induced DNA damage) and directly contribute to its tumour suppressor function. In this review, we provide paramount information on p53, from its discovery, which is an interesting paradigm of science evolution, to potential clinical applications in anti-cancer treatment. The description of the fundamental biology of p53 is enriched by specific information on the structure and function of the protein as well by tumour/host evolutionistic perspectives of its role.
p53肿瘤抑制基因是我们抵御肿瘤转化的主要屏障。它参与许多细胞功能，包括细胞周期阻滞、衰老、DNA修复、凋亡、自噬、细胞代谢、铁死亡、免疫系统调节、活性氧的产生、线粒体功能、基因表达的全局调控、微小RNA等。非常不同的物种（智人、黑腹果蝇、褐家鼠、斑马鱼、家犬、日本壁虎）之间氨基酸序列的高同一性百分比揭示了其至关重要性。它的许多活动使地球上的生命得以存在（例如，修复辐射诱导的DNA损伤），并直接有助于其肿瘤抑制功能。在这篇综述中，我们提供了关于p53的最重要信息，从它的发现（这是科学进化的一个有趣范例）到其在抗癌治疗中的潜在临床应用。对p53基本生物学的描述通过关于该蛋白质结构和功能的特定信息以及其作用的肿瘤/宿主进化观点得到了丰富。
