title: Human papillomavirus type 5 E6 oncoprotein represses the transforming growth factor beta signaling pathway by binding to SMAD3.
abstract: Mechanisms of cellular transformation associated with human papillomavirus type 5 (HPV5), which is responsible for skin carcinomas in epidermodysplasia verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid screening and molecular and cellular biology experiments, we found that HPV5 oncoprotein E6 interacts with SMAD3, a key component in the transforming growth factor beta1 (TGF-beta1) signaling pathway. HPV5 E6 inhibits SMAD3 transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF-beta1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.
authors.affiliation: Unité postulante de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex, France.
authors.forename: Jose-Andres
authors.initials: JA
authors.lastname: Mendoza
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacob
authors.forename: Patricia
authors.initials: P
authors.lastname: Cassonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Favre
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D009856:Oncogene Proteins, Viral; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta