Unravelling Multifaceted p73: From Cell Kinetics to Therapeutics

Abstract

The p73 gene is an important member of the p53 gene family, which includes p53, p63, and p73 genes. The p73 gene was identified by Mckeon's group in 1997 and localised to 1p36 region. The p73 shows a complex interplay with both, p53 and p63 genes. Similar to p63, but unlike p53, p73 has an important role in development especially neuronal development, apart from tumourigenesis. The p73 gene plays a vital role in the development of tumours and exhibits both tumour suppressor and oncogenic behaviour. This dual function is attributed to the presence of the two different variants: TAp73 and ∆Np73 with mutually divergent functions. There exists a dynamic relationship between the multiple p73 isoforms. The p73 has a major role in regulating apoptosis, and Deoxyribonucleic Acid (DNA) damage related cell cycle arrest. It can replace p53 in various apoptotic pathways, as it is capable of transcription of p53 responsive genes. The p73 also participates in myriad processes including angiogenesis, epithelial-mesenchymal transformation, senescence, and maintaining genomic stability. The p73 overexpression has been detected in a number of human cancers. Since it is frequently overexpressed rather than mutated, it is a promising potential candidate for developing therapeutic strategies in various cancers as well as, for predicting the prognosis. It is also implicated in the lack of response to chemotherapeutic drugs. However, the entire spectrum of cellular mechanisms with respect to p73 is still not understood clearly. This article explores the multiple roles of p73, especially in tumour development processes, and also, its recent novel applications in therapeutics