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Journal of Virology, March 2009, p. 2389-2392, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.01690-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Proteasomal Turnover of Hepatitis C Virus Core Protein Is Regulated by Two Distinct Mechanisms: a Ubiquitin-Dependent Mechanism and a Ubiquitin-Independent but PA28{gamma}-Dependent Mechanism{triangledown}

Ryosuke Suzuki,1 Kohji Moriishi,2 Kouichirou Fukuda,1 Masayuki Shirakura,1 Koji Ishii,1 Ikuo Shoji,3 Takaji Wakita,1 Tatsuo Miyamura,1 Yoshiharu Matsuura,2 and Tetsuro Suzuki1*

Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640,1 Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871,2 Division of Microbiology, Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan3

Received 8 August 2008/ Accepted 5 December 2008

We have previously reported on the ubiquitylation and degradation of hepatitis C virus core protein. Here we demonstrate that proteasomal degradation of the core protein is mediated by two distinct mechanisms. One leads to polyubiquitylation, in which lysine residues in the N-terminal region are preferential ubiquitylation sites. The other is independent of the presence of ubiquitin. Gain- and loss-of-function analyses using lysineless mutants substantiate the hypothesis that the proteasome activator PA28{gamma}, a binding partner of the core, is involved in the ubiquitin-independent degradation of the core protein. Our results suggest that turnover of this multifunctional viral protein can be tightly controlled via dual ubiquitin-dependent and -independent proteasomal pathways.


* Corresponding author. Mailing address: Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111. Fax: 81-3-5285-1161. E-mail: tesuzuki{at}nih.go.jp

{triangledown} Published ahead of print on 17 December 2008.


Journal of Virology, March 2009, p. 2389-2392, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.01690-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.