Binding of human papillomavirus 16 E6 to p53 and E6AP is impaired by monoclonal antibodies directed against the second zinc-binding domain of E6
Résumé
The E6 protein of cancer-associated human papillomavirus type 16 (16E6) binds to p53 and, in association with E6AP, promotes its degradation through the ubiquitin-proteasome pathway. The aim of this work was to develop monoclonal antibodies against 16E6 and to test their effect on the binding of 16E6 to p53 and E6AP, and on the degradation of p53. It was shown that an antibody directed against the N terminus of 16E6 inhibited E6AP-dependent binding to p53 and degradation of p53, whereas two different antibodies directed to the second zinc-binding domain of 16E6 reduced 16E6 E6AP-independent binding to p53 and binding to E6AP but not degradation of p53.
Mots clés
Amino Acid Sequence
Animals
Antibodies
Monoclonal/*immunology
COS Cells
Cercopithecus aethiops
Hela Cells
Humans
Molecular Sequence Data
Oncogene Proteins
Viral/chemistry/immunology/*metabolism
Papillomavirus
Human/genetics/*metabolism/pathogenicity
Repressor Proteins/chemistry/immunology/*metabolism
Research Support
Non-U.S. Gov't
Transfection
Tumor Suppressor Protein p53/*metabolism
Ubiquitin-Protein Ligases/*metabolism