Abstract
Hepatitis C virus (HCV) core protein is a multifunctional protein interacting with cellular and viral proteins and promoters. A tetracycline-regulated system was used to generate a HepG2 Tet-Off cell line allowing regulated expression of a full-length (191 aa) and an N(c)-truncated core protein (160 aa). In this system HCV core protein expression activates extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein (MAP) kinase, induces MAP kinase phosphatase MKP-1 expression, and increases cell proliferation. This was accompanied by an activation of c-Jun and ATF-2, but not Elk-1 and c-Fos. Furthermore, AP-1 activation was independent of c-Fos. Full-length and N(c)-truncated HCV core proteins exerted similar effects.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line / drug effects
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Enzyme Activation / drug effects*
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Gene Expression Regulation, Viral
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Hepacivirus / genetics
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Hepacivirus / physiology*
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Humans
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JNK Mitogen-Activated Protein Kinases*
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases / genetics
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Tetracycline / pharmacology
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Viral Core Proteins / metabolism
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Viral Core Proteins / pharmacology*
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Virus Replication / drug effects*
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p38 Mitogen-Activated Protein Kinases
Substances
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Viral Core Proteins
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nucleocapsid protein, Hepatitis C virus
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
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Tetracycline