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KMID : 0921620180480030093
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Journal of Bacteriology and Virology
2018 Volume.48 No. 3 p.93 ~ p.101
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IKKγ Facilitates the Activation of NF-κB by Hepatitis C Virus Core Protein
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Kang Bo-Yeong
Lee So-Yeong
Kim Jin-Ik
Choi Hye-Jung
Joo Woo-Hong
Kim Dong-Wan
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Abstract
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Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV core protein has been shown to modulate various cellular signaling pathways including the nuclear factor κB (NF-κB) pathway which is associated with inflammation, cell proliferation and apoptosis. However, there have been conflicting reports about the effect of HCV core protein on NF-κB pathway, and the mechanism by which the core protein affects NF-κB activity remains nuclear. In this study, the functional interaction of HCV core protein and IκB kinase γ (IKKγ) was investigated using the expression plasmids of core and the components of IKK complex. The data revealed that HCV core protein activates NF-κB. Also, HCV core protein up-regulated the phosphorylation and degradation of IκBα. The activating effect of HCV core protein on NF-κB was synergistically elevated by IKKγ. It was noticed that the N-terminal IKKβ binding site, C-terminal leucine zipper, and zinc finger domains of IKKγ are not necessary for its synergistic effect. HCV core protein and IKKγ appeared to activate NF-κB by up-regulating the IKKβ activity resulting in the degradation of IκBα. As expected, HCV core protein induced the expression of NF-κB-targeted pro-inflammatory genes such as iNOS, IL-1β and IL-6 in the transcription level. These results suggest that HCV core protein induces NF-κB through the interaction with IKKγ and may play a critical role in the development of inflammation and related liver diseases.
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KEYWORD
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Hepatitis C virus, Core protein, NF-κB, IKKγ, Inflammation
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