Abstract
The interferon-alpha (IFN-alpha)-inducible protein IFI44 is associated with hepatitis C virus (HCV) infection, and its function is unknown. We show here in two human melanoma cell lines (ME15 and D10) that transcription starts 4 h after induction, and peak protein levels are reached 24 h after stimulation. We show by immunofluorescence, viral overexpression, and cellular fractionation that IFI44 is a cytoplasmic protein. Overexpression of IFI44 cDNA induces an antiproliferative state in vitro, even in cells that are not responsive to IFN-alpha. IFI44 contains a perfect GTP binding site but has no homology to known GTPases or G proteins. Based on these results, we propose a model in which IFI44 binds intracellular GTP, and this depletion abolishes extracellular signal-regulated kinase (ERK) signaling and results finally in cell cycle arrest.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens / biosynthesis
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Antigens / genetics
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Antigens / metabolism
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Antigens / physiology*
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Cell Cycle / genetics
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Cell Line, Tumor
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Cell Proliferation*
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Cytoskeletal Proteins / biosynthesis
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Cytoskeletal Proteins / physiology*
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Goats
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / genetics
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Growth Inhibitors / physiology*
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Guanosine Triphosphate / metabolism
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HCT116 Cells
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Hepatitis C / metabolism
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Humans
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Interferon-alpha / physiology*
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Molecular Sequence Data
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Protein Binding / genetics
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Rabbits
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Signal Transduction / genetics
Substances
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Antigens
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Cytoskeletal Proteins
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Growth Inhibitors
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IFI44 protein, human
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Interferon-alpha
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Guanosine Triphosphate
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Extracellular Signal-Regulated MAP Kinases