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 λ cl repressor, we demonstrate that the HIV-1 Tat protein specifically interacts with the human p53 protein via the p53 O2 dimerization domain. By random and site-specific mutagenesis, we also identify the residues in Tat and O2 peptides which are involved in this interaction. Two alternative biological consequences are expected to result from Tat-p53 interaction: (i) Tat-O2 interaction inactivates p53 regulation function, thus producing cell transformation; (ii) Tat-O2 interaction favours the formation of p53 dimers, thus leading the cell towards apoptosis.