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Journal of Virology, December 2006, p. 12420-12424, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.02576-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Papillomavirus Type 5 E6 Oncoprotein Represses the Transforming Growth Factor ß Signaling Pathway by Binding to SMAD3{triangledown}

Jose-Andres Mendoza,1,2 Yves Jacob,1 Patricia Cassonnet,1 and Michel Favre1*

Unité postulante de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex, France,1 Departamento de Microbiología y Parasitología Clínicas, Facultad de Medicina, Universidad de Los Andes, Av. Bolívar con calle Unda, Mérida 5101, Venezuela2

Received 12 December 2005/ Accepted 27 September 2006

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 ß1 (TGF-ß1) 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-ß1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.


* Corresponding author. Mailing address: Unité postulante de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex, France. Phone: 33-1-45-68-87-45. Fax: 33-1-45-68-89-66. E-mail: mfavre{at}pasteur.fr.

{triangledown} Published ahead of print on 4 October 2006.


Journal of Virology, December 2006, p. 12420-12424, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.02576-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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