This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Favre-Bonvin, A.
Right arrow Articles by Jalinot, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Favre-Bonvin, A.
Right arrow Articles by Jalinot, P.

 Previous Article  |  Next Article 

Journal of Virology, April 2005, p. 4229-4237, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4229-4237.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Papillomavirus Type 18 E6 Protein Binds the Cellular PDZ Protein TIP-2/GIPC, Which Is Involved in Transforming Growth Factor ß Signaling and Triggers Its Degradation by the Proteasome

Arnaud Favre-Bonvin, Caroline Reynaud,{dagger} Carole Kretz-Remy,{ddagger} and Pierre Jalinot*

Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR 5161, Ecole Normale Supérieure de Lyon, Lyon, France

Received 23 June 2004/ Accepted 28 October 2004

Several viral proteins expressed by DNA or RNA transforming viruses have the particular property of binding via their C-terminal end to various cellular proteins with PDZ domains. This study is focused on the PDZ protein TIP-2/GIPC, which was originally identified in two-hybrid screens performed with two different baits: the human T-cell leukemia virus type 1 Tax oncoprotein and the regulator of G signaling RGS-GAIP. Further studies have shown that TIP-2/GIPC is also able to associate with the cytoplasmic domains of various transmembrane proteins. In this report we show that TIP-2/GIPC interacts with the E6 protein of human papillomavirus type 18 (HPV-18). This event triggers polyubiquitination and proteasome-mediated degradation of the cellular protein. In agreement with this observation, silencing of E6 by RNA interference in HeLa cells causes an increase in the intracellular TIP-2/GIPC level. This PDZ protein has been previously found to be involved in transforming growth factor ß (TGF-ß) signaling by favoring expression of the TGF-ß type III receptor at the cell membrane. In line with this activity of TIP-2/GIPC, we observed that depletion of this protein in HeLa cells hampers induction of the Id3 gene by TGF-ß treatment and also diminishes the antiproliferative effect of this cytokine. Conversely, silencing of E6 increases the expression of Id3 and blocks proliferation of HeLa cells. These results support the notion that HPV-18 E6 renders cells less sensitive to the cytostatic effect of TGF-ß by lowering the intracellular amount of TIP-2/GIPC.

* Corresponding author. Mailing address: Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR 5161, Ecole Normale Supérieure de Lyon, IFR 128 Bioscience Lyon-Gerland, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. Phone: (33)-4-7272-8563. Fax: (33)-4-7272-8080. E-mail: pjalinot{at}ens-lyon.fr.

{dagger} Present address: Institut de Biochimie et Chimie des Protéines, UMR 5086 CNRS UCBL, 69367 Lyon Cedex 07, France.

{ddagger} Present address: Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, 69622 Villeurbanne Cedex, France.

Journal of Virology, April 2005, p. 4229-4237, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4229-4237.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Storrs, C. H., Silverstein, S. J. (2007). PATJ, a Tight Junction-Associated PDZ Protein, Is a Novel Degradation Target of High-Risk Human Papillomavirus E6 and the Alternatively Spliced Isoform 18 E6. J. Virol. 81: 4080-4090 [Abstract] [Full Text]  
  • Handa, K., Yugawa, T., Narisawa-Saito, M., Ohno, S.-i., Fujita, M., Kiyono, T. (2007). E6AP-Dependent Degradation of DLG4/PSD95 by High-Risk Human Papillomavirus Type 18 E6 Protein. J. Virol. 81: 1379-1389 [Abstract] [Full Text]  
  • Wu, J., O'Donnell, M., Gitler, A. D., Klein, P. S. (2006). Kermit 2/XGIPC, an IGF1 receptor interacting protein, is required for IGF signaling in Xenopus eye development. Development 133: 3651-3660 [Abstract] [Full Text]  
  • James, M. A., Lee, J. H., Klingelhutz, A. J. (2006). Human Papillomavirus Type 16 E6 Activates NF-{kappa}B, Induces cIAP-2 Expression, and Protects against Apoptosis in a PDZ Binding Motif-Dependent Manner.. J. Virol. 80: 5301-5307 [Abstract] [Full Text]  
  • Liu, M., Horowitz, A. (2006). A PDZ-binding Motif as a Critical Determinant of Rho Guanine Exchange Factor Function and Cell Phenotype. Mol. Biol. Cell 17: 1880-1887 [Abstract] [Full Text]  
  • Pett, M. R., Herdman, M. T., Palmer, R. D., Yeo, G. S. H., Shivji, M. K., Stanley, M. A., Coleman, N. (2006). Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response. Proc. Natl. Acad. Sci. USA 103: 3822-3827 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»