Comprehensive Roles of TP53 in Cell Signaling, Apoptosis and Carcinogenesis – A Review.

ABSTRACT

TP53 gene is a tumor suppressor gene and it inhibits the emergence of cancerous growth. The signaling of TP53 takes part in the co-ordination of cellular response to various kinds of stress like hypoxia and DNA damage. The downstream signals start to multiple processes such as MTOR (mechanistic target of rapamycin), apoptosis, and the arrest of cell cycle. TP53 becomes inactivated when encounters tumor growth. According to estimation, more than half of all cancers imply the inactivating mutations of TP53, which leads to the expression of mutant p53 protein. An extensive range of cancers carry the mutations of TP53 or certain other defects which deregulate p53 and its cofactors, making this gene a significant and highly studied tumor suppressor gene. Most of the mutations that are found in human cancers are not inherited but are acquired. As p53 protein binds DNA, it triggers another gene to synthesize a protein named p21 inside the cell, which interferes with a cell division-stimulating kinase (cdk2). When p21 forms a complex with cdk2 the cell cannot pass onto the next phase of cell division. Therefore, Mutant p53 can no longer get itself attached to DNA effectively, and as a result, the p21 protein is not made available to function as the 'stop signal' for the division of cell.