The p53 Isoforms as Potential Biomarkers in Different Cancer Entities

The p53 protein is a pivotal tumor suppressor that is mutated in more than half of tumor cases in humans. In addition, its activity/function can be perturbed by various other mechanisms. Existence of two promoters in the TP53 gene and extensive splicing on N- and C-terminus, as well as alternative translation initiation, give rise to numerous p53 protein isoforms. Different p53 protein isoforms can form heterotetramers with canonical full-length p53 or compete in binding target genes' promoters as tetramers which can result in modulation of p53 function. In this review we have gathered the most novel research on the p53 isoform network including the isoforms' expression profiles and biological functions in the most frequent cancer types. The expression of p53 isoforms differs among tumor types and compared with normal tissues, thereby affecting biological processes associated with tumorigenesis, such as apoptosis, cell cycle regulation, migration, senescence, stemness, etc. We also discussed the potential of targeting p53 isoforms by direct mechanisms that can change the ratio between specific isoforms and thus modulate their activity or indirectly by targeting downstream pathways regulated by a specific isoform. More profound understanding of the p53 pathway regulation could contribute to improvement in current therapies.