p53ness in Human Cancers: An Overview

P53, the guardian of the genome, is one of the most studied tumor suppressor gene having the ability to induce cell cycle arrest and/or apoptotic cell death in cancerous cells. Extensive mutation search reveals that 50 % of human cancer can be attributed to mutations in P53 including cancers of Bladder, Breast, Cervix, Colon, Liver, Prostrate & Lungs. P53 is located in the short arm of Chromosome 17 in Humans containing 11 exons. These homologues are sequence specific transcription factors which activate overlapping sets of P53 genes , thus inducing cell cycle arrest or apoptosis. The mutations most sensitive to the loss of function of P53 lie in the exons 5-8 which encode the DNA binding domain of P53. Under normal condition, P53 is generally inactive. But in response to different kind of stresses such as DNA damage, Hypoxia, Oxidative damage etc activates P53 by phosphorylation and dislodging and proteolysis the MDM protein that normally inhibits it during non stressful conditions. However, P53 is not a solitary gene product as it was previously thought. The present study aims to understand the role of p53 gene mutations in Human Cancer.