title: Proteasomal turnover of hepatitis C virus core protein is regulated by two distinct mechanisms: a ubiquitin-dependent mechanism and a ubiquitin-independent but PA28gamma-dependent mechanism.
abstract: 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 PA28gamma, 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.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kohji
authors.initials: K
authors.lastname: Moriishi
authors.forename: Kouichirou
authors.initials: K
authors.lastname: Fukuda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shirakura
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.forename: Ikuo
authors.initials: I
authors.lastname: Shoji
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D002460:Cell Line; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C099558:Ki antigen; D025801:Ubiquitin; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D046988:Proteasome Endopeptidase Complex; D008239:Lysine