Ubiquitin-mediated degradation of hepatitis C virus core protein is regulated by processing at its carboxyl terminus.
Hepatitis C virus core protein, in addition to being a component of the viral capsid, has a number of regulatory functions. Here we showed two bodies of evidence indicating that a fraction of the core protein species is a substrate of the ubiquitin (Ub)-proteasome pathway of targeted proteolysis. First, the core protein processing the C-terminal hydrophobic region is metabolically unstable, and incubation with a proteasome inhibitor led to a significant accumulation of the protein. Second, an in vivo ubiquitylation assay indicates conjugation of multi-Ub chain to the unstable core protein. In contrast, a stable form of core protein, p21, is also able to be ubiquitylated, but it links to a single or only a few Ub moiety. Therefore, processing event(s) at the C-terminal hydrophobic domain of HCV core protein may affect the ubiquitylation pathway, particularly the efficiency of the multi-Ub chain assembly, resulting in stable, matured core proteins.
Suzuki
R
R
Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Tamura
K
K
Li
J
J
Ishii
K
K
Matsuura
Y
Y
Miyamura
T
T
Suzuki
T
T
D001665:Binding Sites; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D014452:Ubiquitins / Q000378:metabolism*; D014758:Viral Core Proteins / Q000096:biosynthesis*
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009097:Multienzyme Complexes; D014452:Ubiquitins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde