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突变型p53的转录调控与肿瘤发生

Transcriptional regulation by mutant p53 and oncogenesis.

作者信息

Santoro Raffaela, Strano Sabrina, Blandino Giovanni

机构信息

Molecular Chemoprevention Group, Molecular Medicine, Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144, Rome, Italy.

出版信息

Subcell Biochem. 2014;85:91-103. doi: 10.1007/978-94-017-9211-0_5.

Abstract

More than half of all human cancers carry p53 gene mutations whose resulting proteins are mostly full-length with a single amino acid change, abundantly present in cancer cells and unable to exert oncosuppressor activities. Frequently, mutant p53 proteins gain oncogenic functions through which they actively contribute to the establishment, the maintenance and the spreading of a given cancer cell. Intense research effort has been devoted to the deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. Here we mainly review the oncogenic transcriptional activity of mutant p53 proteins that mainly occurs through the aberrant cooperation with bona-fide transcription factors and leads to either aberrant up-regulation or down-regulation of selected target genes. Thus, mutant p53 proteins are critical components of oncogenic transcriptional networks that have a profound impact in human cancers.

摘要

超过半数的人类癌症携带p53基因突变,其产生的蛋白质大多为全长,只有一个氨基酸发生变化,大量存在于癌细胞中,且无法发挥抑癌活性。通常,突变型p53蛋白获得致癌功能,通过这些功能它们积极促进特定癌细胞的形成、维持和扩散。人们投入了大量的研究精力来破译突变型p53蛋白功能获得背后的分子机制。在此,我们主要综述突变型p53蛋白的致癌转录活性,这种活性主要通过与真正的转录因子异常协同作用而发生,并导致所选靶基因的异常上调或下调。因此,突变型p53蛋白是致癌转录网络的关键组成部分,对人类癌症有深远影响。

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