Mutational inactivation of the p53 gene products is one of the most common genetic events that occur in human cancer confirming the central role of p53 as a tumour suppressor. The wild type p53 protein acts as a powerful transcription factor binding as many as 300 different promoter sequences in the genome. As a transcription factor, p53 can broadly alter patterns of specific gene expression leading to cell-cycle arrest and/or apoptosis. The transcriptional activity of the p53 protein is precisely regulated and its basal activity is enhanced in cells exposed to a wide variety of stress signals. This stress regulated transactivation function of p53 is driven by its sequence-specific DNA-binding domain and is co-ordinated by specific protein-protein interactions that can be modulated by covalent and non-covalent modifications. The mutant forms of p53 protein are defective in sequence specific DNA-binding because the missense mutation affects one or all of the assembly pathways. Analysis of p53 mutant has shown that different conformational classes of mutants exist and the reactivation of each class requires a different strategy depending on the mechanism of p53 protein misfolding. Potential reactivation of both wild type and mutant p53 protein in vivo raises our hopes of developing anti-cancer drugs useful in combination with sophisticated diagnostics for the treatment of cancer.

        Key words: tumour suppressor, p53, mutation, cancer, cell cycle, apoptosis.