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 Yuksek, K.
Right arrow Articles by Ou, J.-h. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yuksek, K.
Right arrow Articles by Ou, J.-h. J.

 Previous Article  |  Next Article 

Journal of Virology, January 2009, p. 612-621, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.00832-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ubiquitin-Independent Degradation of Hepatitis C Virus F Protein{triangledown}

Kamile Yuksek,1 Wen-ling Chen,1 David Chien,2 and Jing-hsiung James Ou1*

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California,1 Chiron-Novartis Vaccines and Diagnostics, Inc., Emeryville, California2

Received 17 April 2008/ Accepted 13 October 2008

Hepatitis C virus (HCV) F protein is encoded by the +1 reading frame of the viral genome. It overlaps with the core protein coding sequence, and multiple mechanisms for its expression have been proposed. The full-length F protein that is synthesized by translational ribosomal frameshift at codons 9 to 11 of the core protein sequence is a labile protein. By using a combination of genetic, biochemical, and cell biological approaches, we demonstrate that this HCV F protein can bind to the proteasome subunit protein {alpha}3, which reduces the F-protein level in cells in a dose-dependent manner. Deletion-mapping analysis identified amino acids 40 to 60 of the F protein as the {alpha}3-binding domain. This {alpha}3-binding domain of the F protein together with its upstream sequence could significantly destabilize the green fluorescent protein, an otherwise stable protein. Further analyses using an F-protein mutant lacking lysine and a cell line that contained a temperature-sensitive E1 ubiquitin-activating enzyme indicated that the degradation of the F protein was ubiquitin independent. Based on these observations as well as the observation that the F protein could be degraded directly by the 20S proteasome in vitro, we propose that the full-length HCV F protein as well as the F protein initiating from codon 26 is degraded by an ubiquitin-independent pathway that is mediated by the proteasome subunit {alpha}3. The ability of the F protein to bind to {alpha}3 raises the possibility that the HCV F protein may regulate protein degradation in cells.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033. Phone: (323) 442-1720. Fax: (323) 442-1721. E-mail: jamesou{at}hsc.usc.edu

{triangledown} Published ahead of print on 29 October 2008.

Journal of Virology, January 2009, p. 612-621, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.00832-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pena, M. M. O., Melo, S. P., Xing, Y.-Y., White, K., Barbour, K. W., Berger, F. G. (2009). The Intrinsically Disordered N-terminal Domain of Thymidylate Synthase Targets the Enzyme to the Ubiquitin-independent Proteasomal Degradation Pathway. J. Biol. Chem. 284: 31597-31607 [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»