DNA-BINDING ACTIVITY OF WILD-TYPE P53 PROTEIN IS MEDIATED BY THE CENTRAL PART OF THE MOLECULE AND CONTROLLED BY ITS C-TERMINUS

The DNA binding activity of wild type p53 is central to its activity. The ''central'' part of the molecule, where most mutations appear in p rimary human tumors, is the actual DNA binding domain. The C-terminal part was shown to exert a negative effect on the DNA binding activity. In the present study we show that while anti-p53 antibodies recognizi ng the C terminus of the wild type p53 facilitate DNA binding activity , blocking of the wild type specific epitope by specific anti-p53 anti bodies, inhibited the DNA binding activity of the wild type p53 protei n. An alternatively spliced p53 protein exhibits an augmented DNA bind ing activity. The fact that most p53 mutants have lost the wild type p 53 conformation specific epitope, coupled with the observation that bl ocking of this site by binding specific antibodies, prevents the inter action of wild type p53 with DNA, suggests that maintaining the correc t structural conformation of this site is central for DNA binding acti vity. Still, the internal structure of the p53 target and particularly the length of the sequence between the two tandem inverted repeats, i s critical for protein-DNA interaction behavior.