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. H owever, the mechanism of p53 activation in response to DNA damage is u nknown. Recently we have shown that interaction of p53 with sites of D NA damage induces selective proteolytic cleavage of p53, resulting in fragments of 40 and 35 kDa molecular weight. We have also shown that i nteraction of p53 with single-stranded (ss) DNAs results in a differen t pattern of selective proteolysis. This interaction gives a novel 50- kDa protein generated by C-terminal cleavage of the full length protei n and released from the p53-ssDNA complexes. Here we discuss a model w here p53 responds to the DNA damage by generating different sets of th e proteolytic fragments according to the type of the damage.