p53: From Fundamental Biology to Clinical Applications in Cancer.
p53: From Fundamental Biology to Clinical Applications in Cancer.
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作者：
P53抑癌基因是癌症中改变最多的基因。几十年的研究已经证实，它在促进肿瘤现象，包括癌症的发生和发展方面具有至关重要的作用。然而，它对细胞生命具有至关重要的功能。关于这些多方面特性的知识和认识应该是所有科学家的文化背景的一部分。在这篇综述中，我们描述和讨论了P53的多方面作用，从它的发现到在癌症治疗中的临床应用。P53抑癌基因是我们阻止肿瘤转化的主要障碍。它参与了许多细胞功能，包括细胞周期停滞、衰老、DNA修复、凋亡、自噬、细胞代谢、铁下垂、免疫系统调节、活性氧的产生、线粒体功能、基因表达的全球调控、miRNAs等。它的许多活动使地球上的生命得以存活(例如，修复辐射引起的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的重要信息，从它的发现，这是一个有趣的科学进化范例，到在抗癌治疗中的潜在临床应用。关于蛋白质结构和功能的特定信息以及对其作用的肿瘤/宿主进化论观点丰富了对p53基本生物学的描述。
p53 tumour suppressor gene is the most altered in cancer. Several decades of research have established that it is of pivotal importance in prompting neoplastic phenomena, including cancer initiation and progression. However, it has crucial functions for cellular life. Knowledge and awareness about these multifaceted properties should be part of the cultural background of all scientists. In this review, we describe and discuss the multifaceted roles of p53, from its discovery to clinical applications in cancer therapy. 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.
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DOI：
10.1073/pnas.76.5.2420
发表时间：
1979-01-01
影响因子：
11.1
作者：
DELEO, AB;JAY, G;OLD, LJ
通讯作者：
OLD, LJ
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
10.3
作者：
Cortez, Maria Angelica;Ivan, Cristina;Welsh, James W.
通讯作者：
Welsh, James W.
影响因子：
12.4
作者：
Baran, Katherine;Yang, Mao;Green, Douglas R.
通讯作者：
Green, Douglas R.
DOI：
10.1016/j.str.2009.11.011
发表时间：
2010-02-10
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Chen Y;Dey R;Chen L
通讯作者：
Chen L