Tumor-Suppressor Functions of the TP53 Pathway
Tumor-Suppressor Functions of the TP53 Pathway
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DOI：
10.1101/cshperspect.a026062
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发表时间：
2016-05-01
影响因子：
5.4
通讯作者：
Kelly, Gemma L.
中科院分区：
文献类型：
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作者：
Aubrey, Brandon J.;Strasser, Andreas;Kelly, Gemma L.
TP53基因家族的基本生物学重要性通过其可追溯到最早的多细胞生物体的超过10亿年的进化保护而突出。TP53蛋白在细胞对不同应激的反应中提供必要的功能，并保护基因组完整性的维持，这体现在其在肿瘤抑制中的关键作用中。TP53在肿瘤预防中的重要性在人类癌症中得到了例证，其中它是最常检测到的遗传改变。这在动物模型中得到了证实，其中缺陷的TP53基因不可避免地导致癌症发展，而TP53功能的恢复导致由TP53缺失引发的已建立肿瘤的消退。值得注意的是，尽管进行了广泛的研究，TP53作为肿瘤抑制因子的具体机制尚未完全确定。我们回顾了历史和目前的立场，努力了解这些机制，以及它们如何相互补充，在肿瘤抑制。
The fundamental biological importance of the Tp53 gene family is highlighted by its evolutionary conservation for more than one billion years dating back to the earliest multicellular organisms. The TP53 protein provides essential functions in the cellular response to diverse stresses and safeguards maintenance of genomic integrity, and this is manifest in its critical role in tumor suppression. The importance of Tp53 in tumor prevention is exemplified in human cancer where it is the most frequently detected genetic alteration. This is confirmed in animal models, in which a defective Tp53 gene leads inexorably to cancer development, whereas reinstatement of TP53 function results in regression of established tumors that had been initiated by loss of TP53. Remarkably, despite extensive investigation, the specific mechanisms by which TP53 acts as a tumor suppressor are yet to be fully defined. We review the history and current standing of efforts to understand these mechanisms and how they complement each other in tumor suppression.