Abstract
Hepatitis C virus (HCV) is the major etiological agent of blood-borne non-A non-B hepatitis and a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV core protein is a multifunctional protein with regulatory functions in cellular transcription and virus-induced transformation and pathogenesis. Here we report on the identification of a bZIP nuclear transcription protein as an HCV core cofactor for transformation. This bZIP factor, designated LZIP, activates CRE-dependent transcription and regulates cell proliferation. Loss of LZIP function in NIH 3T3 cells triggers morphological transformation and anchorage-independent growth. We show that HCV core protein aberrantly sequesters LZIP in the cytoplasm, inactivates LZIP function and potentiates cellular transformation. Our findings suggest that LZIP might serve a novel cellular tumor suppressor function that is targeted by the HCV core.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Base Sequence
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Basic-Leucine Zipper Transcription Factors
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Cell Line
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Cell Transformation, Viral
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Cyclic AMP Response Element-Binding Protein
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Cytoplasm / metabolism
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DNA Primers / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology
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Dimerization
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G-Box Binding Factors
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HeLa Cells
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Hepacivirus / pathogenicity*
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Humans
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Mice
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Molecular Sequence Data
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Protein Binding
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Protein Structure, Quaternary
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Sequence Homology, Amino Acid
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcriptional Activation
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Viral Core Proteins / physiology*
Substances
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Basic-Leucine Zipper Transcription Factors
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CREB3 protein, human
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Cyclic AMP Response Element-Binding Protein
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DNA Primers
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DNA-Binding Proteins
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G-Box Binding Factors
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Transcription Factors
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Viral Core Proteins