The transcription and expression profile of p53N236S mutant reveals new aspects of gain of function for mutant p53

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, p53N236S , which results in the aggressive progression of tumorigenesis in a knock-in mouse model. To understand the biological significance of the p53N236S mutation, we performed ChIP-on-chip combined with microarray assay to profile the regulated gene expression pattern. We could classify the p53N236S 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 p53N236S . Our data shed light on understanding the difference between this type of low-incidence hotspot p53 mutations and classical hotspot mutations.

Keywords: expression profile; gain of function; p53N236S; transcription profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gain of Function Mutation*
  • Gene Expression Profiling / methods
  • Gene Ontology
  • Gene Regulatory Networks
  • Humans
  • Mice
  • Mutant Proteins / genetics
  • Transcription, Genetic*
  • Transcriptome*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Mutant Proteins
  • Tumor Suppressor Protein p53