Proteolytic cleavage of p53: a model for the activation of p53 in response to DNA damage

p53 is a multifunctional protein that reacts to DNA damage within the cell and regulates the cell growth arrest and/ or apoptotic pathways. However, the mechanism of p53 activation in response to DNA damage is unknown. Recently we have shown that interaction of p53 with sites of DNA damage induces selective proteolytic cleavage of p53, resulting in fragments of 40 and 35 kDa molecular weight. We have also shown that interaction of p53 with single-stranded (ss)DNAs results in a different pattern of selective proteolysis. This interaction gives a novel of 50-kDa protein generated by C-terminal cleavage of the full length protein and released from the p53-ssDNA complexes. Here we discuss a model where p53 responds to the DNA damage by generating different sets of the proteolytic fragments according to the type of the damage.