TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single aminoacid change and are abundantly present in cancer cells. Some of mutant p53 proteins gain oncogenic activities through which actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastatize of cancer cells. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifiers and scaffold proteins. Mutant p53 protein can also transcriptionally regulate the expression of microRNAs, small non-coding RNAs that regulate gene expression at the posttranscriptional level. Each microRNA can putatively target the expression of hundred mRNAs and consequently impact on many cellular functions. Thus, gain of function mutant p53 proteins can exert their oncogenic activities through the modulation of both non-coding and coding regions of human genome.
Keywords: gain of function; microRNAs; mutant p53.