P53: Its Role in Carcinogenesis And Also A Novel Target for Anti-Cancer Therapy

Abstract

p53 is a nuclear binding phosphoprotein, which regulates the gene expressions and controls several key genes involved in gene regulation. It facilitates DNA repair. If the damage is beyond repair, p53 triggers apoptosis of the cell. p53 has been shown to regulate apoptosis in both transcription dependent and independent manner. Various types of genotoxic and non genotoxic stresses can lead to p53 activation like radiations, mutagens like Aflotoxins, benzopyrines, alkylating agents etc. and also the agents which damage mitotic spindle, cause ribonucleotide depletion, hypoxia, heat stroke, exposure to nitric acid etc. These damages are either repaired or apoptosis is triggered. p53 pathways play a critical role in prevention of carcinogenesis. It may turn oncogenic when there is loss of function, dominant negative activity and oncogenic activity of mutant p53. It plays a critical role in oncogenesis by several mechanisms, so targeting p53 is a favorite modality for developing a new approach in cancer therapeutics. The approach includes gene therapy to restore p53 function, inhibition of p53-Mdm interaction, restoration of mutant p53 to wild p53, targeting p53 family proteins, eliminating mutant p53 and p53 based vaccine. It is very interesting to study p53 molecule in this perspective because, this unique molecule, has the property to trigger oncogenesis as well as it can be targeted therapeutically to treat cancers.