Weisz L, Oren M, Rotter V
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Oncogene. 2007 Apr 2;26(15):2202-11. doi: 10.1038/sj.onc.1210294.
In addition to the loss of wild-type p53 activity, a high percentage of tumor cells accumulate mutant p53 protein isoforms. Whereas the hallmark of the wild-type p53 is its tumor suppressor activities, tumor-associated mutant p53 proteins acquire novel functions enabling them to promote a large spectrum of cancer phenotypes. During the last years, it became clear that tumor-associated mutant p53 proteins are not only distinct from the wild-type p53, but they also represent a heterogeneous population of proteins with a variety of structure-function features. One of the major mechanisms underlying mutant p53 gain of function is the ability to regulate gene expression. Although a large number of specific target genes were identified, the molecular basis for this regulation is not fully elucidated. This review describes the present knowledge about the transcriptional activities of mutant p53 and the mechanisms that might underlie its target gene specificity.
除了野生型p53活性丧失外，高比例的肿瘤细胞还积累了突变型p53蛋白异构体。野生型p53的标志是其肿瘤抑制活性，而肿瘤相关的突变型p53蛋白获得了新功能，使其能够促进多种癌症表型。在过去几年中，很明显肿瘤相关的突变型p53蛋白不仅与野生型p53不同，而且它们还代表了具有多种结构-功能特征的异质性蛋白质群体。突变型p53功能获得的主要机制之一是调节基因表达的能力。尽管已鉴定出大量特定的靶基因，但这种调节的分子基础尚未完全阐明。本综述描述了关于突变型p53转录活性及其靶基因特异性潜在机制的现有知识。
