PMID:17108031

Citation	Shirakura, M, Murakami, K, Ichimura, T, Suzuki, R, Shimoji, T, Fukuda, K, Abe, K, Sato, S, Fukasawa, M, Yamakawa, Y, Nishijima, M, Moriishi, K, Matsuura, Y, Wakita, T, Suzuki, T, Howley, PM, Miyamura, T and Shoji, I (2007) E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein. J. Virol. 81:1174-85
Abstract	Hepatitis C virus (HCV) core protein is a major component of viral nucleocapsid and a multifunctional protein involved in viral pathogenesis and hepatocarcinogenesis. We previously showed that the HCV core protein is degraded through the ubiquitin-proteasome pathway. However, the molecular machinery for core ubiquitylation is unknown. Using tandem affinity purification, we identified the ubiquitin ligase E6AP as an HCV core-binding protein. E6AP was found to bind to the core protein in vitro and in vivo and promote its degradation in hepatic and nonhepatic cells. Knockdown of endogenous E6AP by RNA interference increased the HCV core protein level. In vitro and in vivo ubiquitylation assays showed that E6AP promotes ubiquitylation of the core protein. Exogenous expression of E6AP decreased intracellular core protein levels and supernatant HCV infectivity titers in the HCV JFH1-infected Huh-7 cells. Furthermore, knockdown of endogenous E6AP by RNA interference increased intracellular core protein levels and supernatant HCV infectivity titers in the HCV JFH1-infected cells. Taken together, our results provide evidence that E6AP mediates ubiquitylation and degradation of HCV core protein. We propose that the E6AP-mediated ubiquitin-proteasome pathway may affect the production of HCV particles through controlling the amounts of viral nucleocapsid protein.
Links	PubMed PMC1797542 Online version:10.1128/JVI.01684-06
Keywords	Cell Line; Hepacivirus/chemistry; Humans; Ubiquitin-Protein Ligases/metabolism; Ubiquitins/metabolism; Viral Core Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:UBE3A	involved_in	GO:0031398: positive regulation of protein ubiquitination	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:UBE3A		GO:0031398: regulation of protein ubiquitination	ECO:0000314:		P		Figures 4-10: Ubiquitin ligase E6AP binds to HCV (Hepatitis C Virus) core protein to mediate and promote ubiquitination and degradation of the core protein.	complete CACAO 3550

References

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