The transcription and expression profile of p53 N236S mutant reveals new aspects of gain of function for mutant p53.

Missense mutations in the p53 coding gene cause loss and gain of function. We have identified a hotspot mutation, p53(N236S), which results in the aggressive progression of tumorigenesis in a knock-in mouse model. To understand the biological significance of the p53(N236S) mutation, we performed ChIP-on-chip combined with microarray assay to profile the regulated gene expression pat tern. We could classify the p53(N236S) 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(N236S). Our data shed light on understanding the difference between this type of low-incidence hotspot p53 mutations and classical hotspot mutations.