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. 1995 Jun 25;23(12):2137–2146. doi: 10.1093/nar/23.12.2137

cIRF-3, a new member of the interferon regulatory factor (IRF) family that is rapidly and transiently induced by dsRNA.

C E Grant 1, M Z Vasa 1, R G Deeley 1
PMCID: PMC307000  PMID: 7541908

Abstract

In mammals, some of the effects of interferon (IFN) on gene transcription are known to be mediated by a family of IFN-inducible DNA-binding proteins, the IFN regulatory factor (IRF) family, which includes both activators and repressors of transcription. Although IFN activities have been described in many vertebrates, little is known about regulation of IFN- or IFN-stimulated genes in species other than human and mouse. Here, we report the cloning of a chicken cDNA, cIRF-3, encoding a protein with a DNA-binding domain similar to that found in the mammalian IRF family of proteins. Similarity between cIRF-3 and the mammalian IRFs is comparable with that between known members of the family. It is most similar to the IRF proteins ICSBP and ISGF3 gamma but is equally divergent from both. Gel mobility shift assays indicate that cIRF-3 is capable of binding a known IFN-stimulated response element that is conserved between the mammalian and chicken Mx genes. Expression of the cIRF-3 gene can be induced to high levels by poly(I).poly(C). Induction is rapid and transient with no requirement for protein synthesis. Co-treatment of cells with cycloheximide results in superinduction of cIRF-3 mRNA. The structural and regulatory characteristics of cIRF-3 indicate that it is the first example of a non-mammalian IRF protein.

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  1. Abdollahi A., Lord K. A., Hoffman-Liebermann B., Liebermann D. A. Interferon regulatory factor 1 is a myeloid differentiation primary response gene induced by interleukin 6 and leukemia inhibitory factor: role in growth inhibition. Cell Growth Differ. 1991 Aug;2(8):401–407. [PubMed] [Google Scholar]
  2. Ball L. A. Induction of 2'5'-oligoadenylate synthetase activity and a new protein by chick interferon. Virology. 1979 Apr 30;94(2):282–296. doi: 10.1016/0042-6822(79)90462-8. [DOI] [PubMed] [Google Scholar]
  3. Beg A. A., Baldwin A. S., Jr The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 1993 Nov;7(11):2064–2070. doi: 10.1101/gad.7.11.2064. [DOI] [PubMed] [Google Scholar]
  4. Bovolenta C., Driggers P. H., Marks M. S., Medin J. A., Politis A. D., Vogel S. N., Levy D. E., Sakaguchi K., Appella E., Coligan J. E. Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5046–5050. doi: 10.1073/pnas.91.11.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cha Y., Deisseroth A. B. Human interferon regulatory factor 2 gene. Intron-exon organization and functional analysis of 5'-flanking region. J Biol Chem. 1994 Feb 18;269(7):5279–5287. [PubMed] [Google Scholar]
  6. Colgan V., Elbrecht A., Goldman P., Lazier C. B., Deeley R. The avian apoprotein II very low density lipoprotein gene. Methylation patterns of 5' and 3' flanking regions during development and following induction by estrogen. J Biol Chem. 1982 Dec 10;257(23):14453–14460. [PubMed] [Google Scholar]
  7. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  8. Driggers P. H., Ennist D. L., Gleason S. L., Mak W. H., Marks M. S., Levi B. Z., Flanagan J. R., Appella E., Ozato K. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1990 May;87(10):3743–3747. doi: 10.1073/pnas.87.10.3743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elbrecht A., Lazier C. B., Protter A. A., Williams D. L. Independent developmental programs for two estrogen-regulated genes. Science. 1984 Aug 10;225(4662):639–641. doi: 10.1126/science.6740331. [DOI] [PubMed] [Google Scholar]
  10. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fu X. Y. A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s). Cell. 1992 Jul 24;70(2):323–335. doi: 10.1016/0092-8674(92)90106-m. [DOI] [PubMed] [Google Scholar]
  12. Fu X. Y., Kessler D. S., Veals S. A., Levy D. E., Darnell J. E., Jr ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555–8559. doi: 10.1073/pnas.87.21.8555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fujita T., Reis L. F., Watanabe N., Kimura Y., Taniguchi T., Vilcek J. Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9936–9940. doi: 10.1073/pnas.86.24.9936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Garoufalis E., Kwan I., Lin R., Mustafa A., Pepin N., Roulston A., Lacoste J., Hiscott J. Viral induction of the human beta interferon promoter: modulation of transcription by NF-kappa B/rel proteins and interferon regulatory factors. J Virol. 1994 Aug;68(8):4707–4715. doi: 10.1128/jvi.68.8.4707-4715.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gessani S., Di Marzio P., Baglioni C. Activators of protein kinase C enhance accumulation of interferon-beta mRNA in murine cell lines. J Interferon Res. 1989 Oct;9(5):543–550. doi: 10.1089/jir.1989.9.543. [DOI] [PubMed] [Google Scholar]
  16. Gordon J. I., Burns A. T., Christmann J. L., Deeley R. G. Cloning of a double-stranded cDNA that codes for a portion of chicken preproalbumin. A general method for isolating a specific DNA sequence from partially purified mRNA. J Biol Chem. 1978 Dec 10;253(23):8629–8639. [PubMed] [Google Scholar]
  17. Grant C. E., Deeley R. G. Cloning and characterization of chicken YB-1: regulation of expression in the liver. Mol Cell Biol. 1993 Jul;13(7):4186–4196. doi: 10.1128/mcb.13.7.4186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hallquist N. A., Klasing K. C. Serotransferrin, ovotransferrin and metallothionein levels during an immune response in chickens. Comp Biochem Physiol Biochem Mol Biol. 1994 Jul;108(3):375–384. doi: 10.1016/0305-0491(94)90089-2. [DOI] [PubMed] [Google Scholar]
  19. Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989 Aug 25;58(4):729–739. doi: 10.1016/0092-8674(89)90107-4. [DOI] [PubMed] [Google Scholar]
  20. Harada H., Kitagawa M., Tanaka N., Yamamoto H., Harada K., Ishihara M., Taniguchi T. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Science. 1993 Feb 12;259(5097):971–974. doi: 10.1126/science.8438157. [DOI] [PubMed] [Google Scholar]
  21. Harada H., Takahashi E., Itoh S., Harada K., Hori T. A., Taniguchi T. Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system. Mol Cell Biol. 1994 Feb;14(2):1500–1509. doi: 10.1128/mcb.14.2.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Harada H., Willison K., Sakakibara J., Miyamoto M., Fujita T., Taniguchi T. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell. 1990 Oct 19;63(2):303–312. doi: 10.1016/0092-8674(90)90163-9. [DOI] [PubMed] [Google Scholar]
  23. Harroch S., Revel M., Chebath J. Induction by interleukin-6 of interferon regulatory factor 1 (IRF-1) gene expression through the palindromic interferon response element pIRE and cell type-dependent control of IRF-1 binding to DNA. EMBO J. 1994 Apr 15;13(8):1942–1949. doi: 10.1002/j.1460-2075.1994.tb06463.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hoodless P. A., Roy R. N., Ryan A. K., Haché R. J., Vasa M. Z., Deeley R. G. Developmental regulation of specific protein interactions with an enhancerlike binding site far upstream from the avian very-low-density apolipoprotein II gene. Mol Cell Biol. 1990 Jan;10(1):154–164. doi: 10.1128/mcb.10.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hoodless P. A., Ryan A. K., Schrader T. J., Deeley R. G. Characterization of liver-enriched proteins binding to a developmentally demethylated site flanking the avian apoVLDLII gene. DNA Cell Biol. 1992 Dec;11(10):755–765. doi: 10.1089/dna.1992.11.755. [DOI] [PubMed] [Google Scholar]
  26. Kanno Y., Kozak C. A., Schindler C., Driggers P. H., Ennist D. L., Gleason S. L., Darnell J. E., Jr, Ozato K. The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds. Mol Cell Biol. 1993 Jul;13(7):3951–3963. doi: 10.1128/mcb.13.7.3951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kawaguchi T., Nomura K., Hirayama Y., Kitagawa T. Establishment and characterization of a chicken hepatocellular carcinoma cell line, LMH. Cancer Res. 1987 Aug 15;47(16):4460–4464. [PubMed] [Google Scholar]
  28. Kirchhoff S., Schaper F., Hauser H. Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes. Nucleic Acids Res. 1993 Jun 25;21(12):2881–2889. doi: 10.1093/nar/21.12.2881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  30. Levy D. E., Kessler D. S., Pine R., Darnell J. E., Jr Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro. Genes Dev. 1989 Sep;3(9):1362–1371. doi: 10.1101/gad.3.9.1362. [DOI] [PubMed] [Google Scholar]
  31. Meegan J. M., Marcus P. I. Double-stranded ribonuclease coinduced with interferon. Science. 1989 Jun 2;244(4908):1089–1091. doi: 10.1126/science.2471268. [DOI] [PubMed] [Google Scholar]
  32. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  33. Nelson N., Marks M. S., Driggers P. H., Ozato K. Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Mol Cell Biol. 1993 Jan;13(1):588–599. doi: 10.1128/mcb.13.1.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pine R., Decker T., Kessler D. S., Levy D. E., Darnell J. E., Jr Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either. Mol Cell Biol. 1990 Jun;10(6):2448–2457. doi: 10.1128/mcb.10.6.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Politis A. D., Ozato K., Coligan J. E., Vogel S. N. Regulation of IFN-gamma-induced nuclear expression of IFN consensus sequence binding protein in murine peritoneal macrophages. J Immunol. 1994 Mar 1;152(5):2270–2278. [PubMed] [Google Scholar]
  36. Politis A. D., Sivo J., Driggers P. H., Ozato K., Vogel S. N. Modulation of interferon consensus sequence binding protein mRNA in murine peritoneal macrophages. Induction by IFN-gamma and down-regulation by IFN-alpha, dexamethasone, and protein kinase inhibitors. J Immunol. 1992 Feb 1;148(3):801–807. [PubMed] [Google Scholar]
  37. Sabe H., Knudsen B., Okada M., Nada S., Nakagawa H., Hanafusa H. Molecular cloning and expression of chicken C-terminal Src kinase: lack of stable association with c-Src protein. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2190–2194. doi: 10.1073/pnas.89.6.2190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schindler C., Shuai K., Prezioso V. R., Darnell J. E., Jr Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992 Aug 7;257(5071):809–813. doi: 10.1126/science.1496401. [DOI] [PubMed] [Google Scholar]
  39. Schumacher B., Bernasconi D., Schultz U., Staeheli P. The chicken Mx promoter contains an ISRE motif and confers interferon inducibility to a reporter gene in chick and monkey cells. Virology. 1994 Aug 15;203(1):144–148. doi: 10.1006/viro.1994.1464. [DOI] [PubMed] [Google Scholar]
  40. Sekellick M. J., Ferrandino A. F., Hopkins D. A., Marcus P. I. Chicken interferon gene: cloning, expression, and analysis. J Interferon Res. 1994 Apr;14(2):71–79. doi: 10.1089/jir.1994.14.71. [DOI] [PubMed] [Google Scholar]
  41. Sensel M. G., Binder R., Lazier C. B., Williams D. L. Reactivation of apolipoprotein II gene transcription by cycloheximide reveals two steps in the deactivation of estrogen receptor-mediated transcription. Mol Cell Biol. 1994 Mar;14(3):1733–1742. doi: 10.1128/mcb.14.3.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  43. Sims S. H., Cha Y., Romine M. F., Gao P. Q., Gottlieb K., Deisseroth A. B. A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter. Mol Cell Biol. 1993 Jan;13(1):690–702. doi: 10.1128/mcb.13.1.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tanaka N., Ishihara M., Kitagawa M., Harada H., Kimura T., Matsuyama T., Lamphier M. S., Aizawa S., Mak T. W., Taniguchi T. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell. 1994 Jun 17;77(6):829–839. doi: 10.1016/0092-8674(94)90132-5. [DOI] [PubMed] [Google Scholar]
  45. Tanaka N., Kawakami T., Taniguchi T. Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Mol Cell Biol. 1993 Aug;13(8):4531–4538. doi: 10.1128/mcb.13.8.4531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tanaka N., Taniguchi T. Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system. Adv Immunol. 1992;52:263–281. doi: 10.1016/s0065-2776(08)60877-9. [DOI] [PubMed] [Google Scholar]
  47. Thacore H. R., Lin H. Y., Davis P. J., Schoenl M. Effect of protein kinase C inhibitors on interferon-beta production by viral and non-viral inducers. J Gen Virol. 1990 Dec;71(Pt 12):2833–2839. doi: 10.1099/0022-1317-71-12-2833. [DOI] [PubMed] [Google Scholar]
  48. Veals S. A., Santa Maria T., Levy D. E. Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity. Mol Cell Biol. 1993 Jan;13(1):196–206. doi: 10.1128/mcb.13.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Veals S. A., Schindler C., Leonard D., Fu X. Y., Aebersold R., Darnell J. E., Jr, Levy D. E. Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol Cell Biol. 1992 Aug;12(8):3315–3324. doi: 10.1128/mcb.12.8.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Velazquez L., Fellous M., Stark G. R., Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992 Jul 24;70(2):313–322. doi: 10.1016/0092-8674(92)90105-l. [DOI] [PubMed] [Google Scholar]
  51. Visvanathan K. V., Goodbourn S. Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter. EMBO J. 1989 Apr;8(4):1129–1138. doi: 10.1002/j.1460-2075.1989.tb03483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Watanabe N., Sakakibara J., Hovanessian A. G., Taniguchi T., Fujita T. Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis. Nucleic Acids Res. 1991 Aug 25;19(16):4421–4428. doi: 10.1093/nar/19.16.4421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Weisz A., Marx P., Sharf R., Appella E., Driggers P. H., Ozato K., Levi B. Z. Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. J Biol Chem. 1992 Dec 15;267(35):25589–25596. [PubMed] [Google Scholar]
  54. Wick G., Krömer G., Neu N., Fässler R., Ziemiecki A., Müller R. G., Ginzel M., Béládi I., Kühr T., Hála K. The multi-factorial pathogenesis of autoimmune disease. Immunol Lett. 1987 Dec;16(3-4):249–257. doi: 10.1016/0165-2478(87)90154-4. [DOI] [PubMed] [Google Scholar]
  55. Wiskocil R., Bensky P., Dower W., Goldberger R. F., Gordon J. I., Deeley R. G. Coordinate regulation of two estrogen-dependent genes in avian liver. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4474–4478. doi: 10.1073/pnas.77.8.4474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Yamada G., Ogawa M., Akagi K., Miyamoto H., Nakano N., Itoh S., Miyazaki J., Nishikawa S., Yamamura K., Taniguchi T. Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):532–536. doi: 10.1073/pnas.88.2.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Yoshida I., Marcus P. I. Interferon induction by viruses. XX. Acid-labile interferon accounts for the antiviral effect induced by poly(rI).poly(rC) in primary chick embryo cells. J Interferon Res. 1990 Oct;10(5):461–468. doi: 10.1089/jir.1990.10.461. [DOI] [PubMed] [Google Scholar]
  58. Yu-Lee L. Y., Hrachovy J. A., Stevens A. M., Schwarz L. A. Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells. Mol Cell Biol. 1990 Jun;10(6):3087–3094. doi: 10.1128/mcb.10.6.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Zinn K., Keller A., Whittemore L. A., Maniatis T. 2-Aminopurine selectively inhibits the induction of beta-interferon, c-fos, and c-myc gene expression. Science. 1988 Apr 8;240(4849):210–213. doi: 10.1126/science.3281258. [DOI] [PubMed] [Google Scholar]
  60. Zöller B., Ozato K., Kroemer G., Auffray C., Jungwirth C. Interferon induction of chicken MHC class I gene expression: phylogenetic conservation of the interferon-responsive element. Virology. 1992 Nov;191(1):141–149. doi: 10.1016/0042-6822(92)90175-o. [DOI] [PubMed] [Google Scholar]

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