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p53 突变体的转录和表达谱揭示了突变型 p53 获得功能的新方面。

The transcription and expression profile of p53 mutant reveals new aspects of gain of function for mutant p53.

机构信息

Lab of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science & Technology, Chenggong County, Kunming, China.

School of Physical Education, Yuxi Normal University, Hongta District, Yuxi, China.

出版信息

FEBS Lett. 2018 Sep;592(18):3183-3197. doi: 10.1002/1873-3468.13223. Epub 2018 Aug 29.

Abstract

Missense mutations in the p53 coding gene cause loss and gain of function. We have identified a hotspot mutation, p53 , which results in the aggressive progression of tumorigenesis in a knock-in mouse model. To understand the biological significance of the p53 mutation, we performed ChIP-on-chip combined with microarray assay to profile the regulated gene expression pattern. We could classify the p53 mutant function into six categories. Among these, we reveal a new aspect of gain of function, the enhancement of wild-type p53 function, which has not been reported previously. We also show the existence of residual wild-type p53 function in p53 . Our data shed light on understanding the difference between this type of low-incidence hotspot p53 mutations and classical hotspot mutations.

摘要

错义突变导致 p53 编码基因突变,导致功能丧失和获得。我们已经确定了一个热点突变 p53 ,它导致了敲入小鼠模型中肿瘤发生的侵袭性进展。为了了解 p53 突变的生物学意义,我们进行了 ChIP-on-chip 与微阵列分析相结合的研究,以分析受调控的基因表达模式。我们可以将 p53 突变体的功能分为六类。在这些功能中,我们揭示了一个新的获得性功能,即增强野生型 p53 功能,这是以前没有报道过的。我们还显示了 p53 中残留的野生型 p53 功能的存在。我们的数据为理解这种低发生率热点 p53 突变与经典热点突变之间的差异提供了线索。

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