Abstract
The complex, partially overlapping, cellular responses to IFN type I (IFN-alpha and -beta) and IFN type II (IFN-gamma) involve several hundred genes that can be largely classified in terms of specific cellular programs functional in innate and adaptive immunity. Among these programs are previously unconsidered mechanisms of cell-autonomous resistance against various pathogens mediated by dedicated, largely novel families of GTPases. We report here the identification and characterization of a new GTPase family that contributes to the cellular response to both type I and type II IFNs. We name this family the very large inducible GTPases (VLIGs). The prototype VLIG, VLIG-1, is a strongly IFN-inducible, soluble, cytosolic and nuclear protein of 280 kDa. The open reading frame of VLIG-1 is encoded on a single very large exon, and outside the canonical GTP-binding motifs, sequence and structural prediction suggest a unique family without significant relationship to other known protein families. Within the GTPase superfamily the VLIG family is more closely related to IFN-inducible GTPases mediating cell-autonomous resistance than to other GTPase families. In addition, we provide evidence that VLIG-1 is polymorphic in mice of different genetic backgrounds and is a member of a small gene family on mouse chromosome 7 with a conserved homologue located on human chromosome 11.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cells, Cultured
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Chromosome Mapping
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Chromosomes, Human, Pair 11 / genetics
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Cloning, Molecular / methods
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Cytokines / pharmacology
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DNA-Binding Proteins / physiology
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GTP Phosphohydrolases / biosynthesis*
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GTP Phosphohydrolases / genetics*
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GTP Phosphohydrolases / isolation & purification
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GTP Phosphohydrolases / metabolism
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Gene Expression Regulation / immunology*
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Guanine Nucleotides / metabolism
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Guanosine Triphosphate / metabolism
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Humans
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Immunity, Innate / genetics
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Interferon Regulatory Factor-1
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Interferon-gamma / pharmacology
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Interferons / physiology*
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Listeriosis / enzymology
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Listeriosis / immunology
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Liver / enzymology
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Liver / microbiology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Multigene Family
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Nuclear Proteins / biosynthesis*
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Nuclear Proteins / genetics*
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Nuclear Proteins / isolation & purification
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Nuclear Proteins / metabolism
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Organ Specificity / genetics
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Organ Specificity / immunology
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Phosphoproteins / physiology
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Polymorphism, Genetic
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Protein Binding
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Protein Structure, Tertiary
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RNA, Messenger / biosynthesis
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Species Specificity
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Subcellular Fractions / metabolism
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Transcription Factors / physiology
Substances
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Cytokines
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DNA-Binding Proteins
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Guanine Nucleotides
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IRF1 protein, human
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Interferon Regulatory Factor-1
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Irf1 protein, mouse
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Nuclear Proteins
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Phosphoproteins
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RNA, Messenger
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Transcription Factors
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Interferon-gamma
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Guanosine Triphosphate
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Interferons
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GTP Phosphohydrolases
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GVINP1 protein, human
Associated data
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GENBANK/AY167972
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GENBANK/AY167973
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GENBANK/AY167974