Binding of human papillomavirus 16 E6 to p53 and E6AP is impaired by monoclonal antibodies directed against the second zinc-binding domain of E6.
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.
Lagrange
Magali
M
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Charbonnier
Sebastian
S
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Orfanoudakis
Georges
G
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Robinson
Philip
P
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Zanier
Katia
K
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Masson
Murielle
M
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Lutz
Yves
Y
IGBMC, CNRS/INSERM/ULP, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France.
Trave
Gilles
G
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Weiss
Etienne
E
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
Deryckere
François
F
UMR7100, Ecole Supérieure de Biotechnologie de Strasbourg, Pole API, boulevard Sébastien Brant, 67412 Illkirch Cedex, France.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D012097:Repressor Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases