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 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.
Longo
F
F
Dipartimento di Biopatologia Umana Sezione di Biologia Cellulare Università di Roma La Sapienza, Rome, Italy.
Marchetti
M A
MA
Castagnoli
L
L
Battaglia
P A
PA
Gigliani
F
F
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins; D015696:Gene Products, tat / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011897:Random Allocation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry; D015183:Restriction Mapping; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D054322:tat Gene Products, Human Immunodeficiency Virus