European Journal of Biomedical and Pharmaceutical Sciences

P53: THE GUARDIAN OF GENOME, APOPTOSIS, AND ITS ROLE IN CARCINOGENESIS

Dr Sujan Narayan Agrawal.*, Dr Kamlesh Dhruv and Dr (Smt) Sunita Meshram

ABSTRACT

The p53 protein also labeled as tumor protein 53 (or TP53) is one of the best known tumor suppressor protein encoded by the tumor suppressor gene TP53, located in the short arm of chromosome 17.(17 P13.1). Since its discovery many studies have looked into its function and its role in cancer. It is not only involved in the induction of apoptosis but is also a key player in cell cycle regulation, development, differentiation, gene amplification, DNA recombination, chromosomal segregation and cellular senescence and so, it is called “the guardian of genome”. It is considered as the “ultimate tumour suppressor gene”, the function of which is essentially to protect the cell against the occurrence and development of cancers. The term apoptosis is derived from the Greek word meaning “dropping off “ and refers to the falling of leaves from tree in Autumn. The biochemical changes seen during apoptosis consist of activation of caspase, DNA and protein breakdown membrane changes and recognition by phagocytic cells. Senescence has already been emerged as an important contributor to TP53 tumor suppressor activity. Another tumor suppressor activity of p53, which is still poorly understood, is its ability to modulate cell migration. The altered cellular movement, loss of p53, increased cell motility contributes to tumor invasiveness. Carcinogenesis is a result of genetic changes in which normal cell are transformed to malignant cell. The mechanism by which evasion occurs is due to disrupted balance of pro-apoptotic and anti-apoptotic proteins, reduced caspase function, impaired death receptor signaling and or senescence. It is well known that p53 acts biochemically as a transcription factor and biologically as a powerful tumor suppressor. It has got a central role in cancer prevention and suppression, and in chemo-sensitization or radio-sensitization.

Keywords: Guardian of Genome, Apoptosis, Senescence, BCL-2, Oncogene, Carcinogenesis