NDLI: Hepatitis C Virus Core Protein Activates Nuclear Factor κB-dependent Signaling through Tumor Necrosis Factor Receptor-associated Factor

Content Provider	Journal of Biological Chemistry (JBC)
Author	Yoshida, Hideo Kato, Naoya Shiratori, Yasushi Otsuka, Motoyuki Maeda, Shin Kato, Jun Omata, Masao
Abstract	Hepatitis C virus (HCV) core protein, a viral nucleocapsid, has been shown to affect various intracellular events including the nuclear factor κB (NF-κB) signaling supposedly associated with inflammatory response, cell proliferation, and apoptosis. In order to elucidate the effect of HCV core protein on the NF-κB signaling in HeLa and HepG2 cells, a reporter assay was utilized. HCV core protein significantly activated NF-κB signaling in a dose-dependent manner not only in HeLa and HepG2 cells transiently transfected with core protein expression plasmid, but also in HeLa cells induced to express core protein under the control of doxycycline. HCV core protein increased the DNA binding affinity of NF-κB in the electrophoretic mobility shift assay. Acetyl salicylic acid, an IKKβ-specific inhibitor, and dominant negative form of IKKβ significantly blocked NF-κB activation by HCV core protein, suggesting HCV core protein activates the NF-κB pathway mainly through IKKβ. Moreover, the dominant negative forms of TRAF2/6 significantly blocked activation of the pathway by HCV core protein, suggesting HCV core protein mimics proinflammatory cytokine activation of the NF-κB pathway through TRAF2/6. In fact, HCV core protein activated interleukin-1β promoter mainly through NF-κB pathway. Therefore, this function of HCV core protein may play an important role in the inflammatory reaction induced by this hepatotropic virus.
Related Links	http://www.jbc.org/content/276/19/16399.abstract
Ending Page	16405
Starting Page	16399
Page Count	7
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	19
Volume Number	276
DOI	10.1074/jbc.M006671200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2001-05-11
Access Restriction	Open
Subject Keyword	Hepatitis C virus (HCV) Amino acid(s) (aa) Activator protein-1 (AP-1) Electrophoretic mobility shift assay (EMSA) IκB kinase (IKK) Interleukin (IL) Latent membrane protein-1 (LMP-1) Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEKK1) Nuclear factor κB (NF-κB) Nucleotide(s) (nt) Nuclear factor κB inducing kinase (NIK) Receptor interacting protein (RIP) Tumor necrosis factor (TNF) Tumor necrosis factor receptor 1 (TNFR1) Tumor necrosis factor receptor-associated death domain (TRADD) Tumor necrosis factor receptor-associated factor (TRAF) Hemagglutinin (HA) Polymerase chain reaction (PCR) Phosphate-buffered saline (PBS) MECHANISMS OF SIGNAL TRANSDUCTION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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