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© Research
Publication : Journal of virology

Human papillomavirus type 5 E6 oncoprotein represses the transforming growth factor beta signaling pathway by binding to SMAD3

Team: Archived: Virus interactomics
Team: Archived: Molecular Genetics of RNA Viruses
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of virology - 04 Oct 2006

Mendoza JA, Jacob Y, Cassonnet P, Favre M

Link to Pubmed [PMID] – 17020941

J. Virol. 2006 Dec;80(24):12420-4

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.