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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.
-Dependent Mechanism
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
, 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.
Published ahead of print on 17 December 2008.
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