Peptides derived from the two regulatory domains of p53 are recognized by two p53-activating antibodies.
The C-terminus of the transcription factor p53 seems to play an important role by controlling the specific DNA-binding activity, which is directly associated with sensing damaged DNA. Another region located in the N-terminus of the protein has also been shown to regulate the DNA-binding activity of the protein. This activity can be promoted by peptides derived from these two negative regulatory regions or by binding of antibodies directed against the C-terminus of the p53 protein. Using both phage display peptide and multiple peptide synthesis technologies, we demonstrated that mAbs HR231 and Pab421, two p53-activating antibodies, recognize peptides derived from the C-terminus of p53, as previously described, but also peptides from the N-terminus of the protein, suggesting that these peptides are part of a conformational epitope. Furthermore, the sequences of these peptides are located in the two negative regulatory regions identified on the p53 protein, which is consistent with the biological activity of mAbs HR231 and Pab421.
CNRS-UMR 5094, CRLC Val d'Aurelle/Bât Recherche, Rue de la Croix Verte, 34298 Montpellier Cedex 5, France.
Jean-Michel
JM
Portefaix
Maguy Del
MD
Rio
Claude
C
Granier
Françoise
F
Roquet
Bernard
B
Pau
Isabelle
I
Navarro-Teulon
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000819:agonists* / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D010446:Peptide Fragments; D019151:Peptide Library; D016159:Tumor Suppressor Protein p53