Monoclonal antibodies raised against Xenopus p53 interact with human p73.
The p53 tumor suppressor gene belongs to a multigene family that includes two paralogues, p63 and p73. The structure of the p63 and p73 genes is quite similar, but both have common activities with p53, such as DNA binding and transactivation. Both p53 and p73 bind to mdm2, but only p53 is degraded through the activity of mdm2. p63 neither binds to nor is degraded by mdm2 despite important conservation in the key interacting residues. Using a panel of monoclonal antibodies raised against human and Xenopus p53, we have been able to find several antibodies that cross-react strongly with human p73. These antibodies react both with exogenous p73 expressed in mammalian cells and with endogenous p73. Interestingly, all these antibodies react with the same epitope localized in the amino-terminus of p53, but have no cross-reaction with p63. This epitope corresponds to the exact mdm2 binding site to p53. These antibodies inhibit the interaction between either p53 or p73 and mdm2, and may be useful tools for the study of these proteins. Furthermore, our studies suggest that there exist specific spatial requirements for the interaction between p53 or p73 and mdm2.
Le Bras
Morgane
M
Laboratoire de Génotoxicologie des Tumeurs, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
Delattre
Valérie
V
Bensaad
Karim
K
Blandino
Giovanni
G
Soussi
Thierry
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D015153:Blotting, Western; D003429:Cross Reactions / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D019084:Fluorescent Antibody Technique, Indirect; D016147:Genes, Tumor Suppressor; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D007106:Immune Sera; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C488640:TP63 protein, Xenopus; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins