A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein.
The cloning and functional characterization of a novel interferon regulatory factor (IRF), IRF-10, are described. IRF-10 is most closely related to IRF-4 but differs in both its constitutive and inducible expression. The expression of IRF-10 is inducible by interferons (IFNs) and by concanavalin A. In contrast to that of other IRFs, the inducible expression of IRF-10 is characterized by delayed kinetics and requires protein synthesis, suggesting a unique role in the later stages of an antiviral defense. Accordingly, IRF-10 is involved in the upregulation of two primary IFN-gamma target genes (major histocompatibility complex [MHC] class I and guanylate-binding protein) and interferes with the induction of the type I IFN target gene for 2',5'-oligo(A) synthetase. IRF-10 binds the interferon-stimulated response element site of the MHC class I promoter. In contrast to that of IRF-1, which has some of the same functional characteristics, the expression of IRF-10 is not cytotoxic for fibroblasts or B cells. The expression of IRF-10 is induced by the oncogene v-rel, the proto-oncogene c-rel, and IRF-4 in a tissue-specific manner. Moreover, v-Rel and IRF-4 synergistically cooperate in the induction of IRF-10 in fibroblasts. The level of IRF-10 induction in lymphoid cell lines by Rel proteins correlates with Rel transformation potential. These results suggest that IRF-10 plays a role in the late stages of an immune defense by regulating the expression some of the IFN-gamma target genes in the absence of a cytotoxic effect. Furthermore, IRF-10 expression is regulated, at least in part, by members of the Rel/NF-kappa B and IRF families.
Nehyba
Jirí
J
Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712-1095,USA.
Hrdlicková
Radmila
R
Burnside
Joan
J
Bose
Henry R
HR
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D002642:Chick Embryo; D002645:Chickens; D003001:Cloning, Molecular; D003208:Concanavalin A / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D015870:Gene Expression; D005805:Genes, MHC Class I; D020573:Genes, rel; D050835:Interferon Regulatory Factors; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
D030161:Avian Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D014157:Transcription Factors; C455582:interferon regulatory factor-10, Gallus gallus; D003208:Concanavalin A; D007372:Interferons