Brosh Ran, Rotter Varda
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nat Rev Cancer. 2009 Oct;9(10):701-13. doi: 10.1038/nrc2693. Epub 2009 Aug 20.
Ample data indicate that mutant p53 proteins not only lose their tumour suppressive functions, but also gain new abilities that promote tumorigenesis. Moreover, recent studies have modified our view of mutant p53 proteins, portraying them not as inert mutants, but rather as regulated proteins that influence the cancer cell transcriptome and phenotype. This influence is clinically manifested as association of TP53 mutations with poor prognosis and drug resistance in a growing array of malignancies. Here, we review recent studies on mutant p53 regulation, gain-of-function mechanisms, transcriptional effects and prognostic association, with a focus on the clinical implications of these findings.
大量数据表明,突变型p53蛋白不仅失去了其肿瘤抑制功能,还获得了促进肿瘤发生的新能力。此外,最近的研究改变了我们对突变型p53蛋白的看法,不再将它们视为无活性的突变体,而是将它们描绘成影响癌细胞转录组和表型的受调控蛋白。这种影响在临床上表现为TP53突变与越来越多恶性肿瘤的不良预后和耐药性相关。在这里,我们综述了关于突变型p53调控、功能获得机制、转录效应和预后关联的最新研究,重点关注这些发现的临床意义。