ABSTRACT
The p53 tumor suppressor protein, first discovered in 1979, acts as a major node in a complex signalling pathway evolved to sense a broad range of cellular stresses such as DNA damage, oncogene activation, viral infection and ribonucleotide depletion. The p53 network, normally switched ‘off’, is activated by such cellular stresses that can alter normal cell cycle progression or induce mutations of the genome leading to oncogenic transformation. Activated p53 protein stops the cell cycle or, in many cases, switches ‘on’ the programmed cell death (apoptosis) pathways forcing damaged cells to commit suicide.1 The p53 protein therefore prevents the multiplication of stressed cells that are more likely than undamaged cells both to contain mutations and exhibitabnormal cellular growth. Hence, the p53 protein, the guardian of the genome, is a critical inhibitor of tumour development explaining why it is the most frequently mutated gene in human cancers.
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