A NOVEL-APPROACH TO PROTEIN-PROTEIN INTERACTION - COMPLEX-FORMATION BETWEEN THE P53 TUMOR-SUPPRESSOR AND THE HIV TAT PROTEINS

By using a novel genetic approach, based on the properties of lambda c l repressor, we demonstrate that the HIV-1 Tat protein specifically in teracts with the human p53 protein via the p53 O2 dimerization domain. By random and site-specific mutagenesis, we also identify the residue s in Tat and O2 peptides which are involved in this interaction. Two a lternative biological consequences are expected to result from Tat-p53 interaction: (i) Tat-O2 interaction inactivates p53 regulation functi on, thus producing cell transformation; (ii) Tat-O2 interaction favour s the formation of p53 dimers, thus leading the cell towards apoptosis . (C) 1995 Academic Press, Inc.