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突变型p53:一、无人、十万

Mutant p53: One, No One, and One Hundred Thousand.

作者信息

Walerych Dawid, Lisek Kamil, Del Sal Giannino

机构信息

Laboratorio Nazionale CIB, Area Science Park Padriciano , Trieste , Italy.

Laboratorio Nazionale CIB, Area Science Park Padriciano, Trieste, Italy; Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy.

出版信息

Front Oncol. 2015 Dec 21;5:289. doi: 10.3389/fonc.2015.00289. eCollection 2015.

Abstract

Encoded by the mutated variants of the TP53 tumor suppressor gene, mutant p53 proteins are getting an increased experimental support as active oncoproteins promoting tumor growth and metastasis. p53 missense mutant proteins are losing their wild-type tumor suppressor activity and acquire oncogenic potential, possessing diverse transforming abilities in cell and mouse models. Whether various mutant p53s differ in their oncogenic potential has been a matter of debate. Recent discoveries are starting to uncover the existence of mutant p53 downstream programs that are common to different mutant p53 variants. In this review, we discuss a number of studies on mutant p53, underlining the advantages and disadvantages of alternative experimental approaches that have been used to describe the numerous mutant p53 gain-of-function activities. Therapeutic possibilities are also discussed, taking into account targeting either individual or multiple mutant p53 proteins in human cancer.

摘要

突变型p53蛋白由肿瘤抑制基因TP53的突变变体编码,作为促进肿瘤生长和转移的活性癌蛋白,它们获得了越来越多的实验支持。p53错义突变蛋白正在丧失其野生型肿瘤抑制活性,并获得致癌潜力,在细胞和小鼠模型中具有多种转化能力。各种突变型p53的致癌潜力是否不同一直是一个有争议的问题。最近的发现开始揭示不同突变型p53变体共有的突变型p53下游程序的存在。在这篇综述中,我们讨论了一些关于突变型p53的研究,强调了用于描述众多突变型p53功能获得活性的替代实验方法的优缺点。还讨论了治疗可能性,同时考虑到在人类癌症中靶向单个或多个突变型p53蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/4685664/6761d5b47bfd/fonc-05-00289-g001.jpg

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