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Interferon regulatory factor 8
Identifiers
Symbols IRF8; H-ICSBP; ICSBP; ICSBP1; IRF-8
External IDs OMIM601565 MGI96395 HomoloGene1629 GeneCards: IRF8 Gene
RNA expression pattern
PBB GE IRF8 204057 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3394 15900
Ensembl ENSG00000140968 ENSMUSG00000041515
UniProt Q02556 Q3TZQ3
RefSeq (mRNA) NM_002163 NM_008320
RefSeq (protein) NP_002154 NP_032346
Location (UCSC) Chr 16:
84.49 - 84.51 Mb
Chr 8:
123.62 - 123.64 Mb
PubMed search [1] [2]

Interferon regulatory factor 8, also known as IRF8 and ICSBP, is a protein which in humans is encoded by the IRF8 gene.[1][2][3]

Contents

Function

Interferon consensus sequence-binding protein (ICSBP) is a transcription factor of the interferon regulatory factor (IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-α and IFN-β. IRF family proteins also control expression of IFN-α and IFN-β-regulated genes that are induced by viral infection.[1].
Mouse IFN-producing cells (mIPCs) were absent in all lymphoid organs from ICSBP KO mice, as revealed by lack of CD11c(low)B220(+)Ly6C(+)CD11b(-) cells. In parallel, CD11c(+) cells isolated from ICSBP KO spleens were unable to produce type I IFNs in response to viral stimulation. ICSBP KO mice also displayed a marked reduction of the DC subset expressing the CD8alpha marker (CD8alpha(+) DCs) in spleen, lymph nodes, and thymus. Moreover, ICSBP-deficient CD8alpha(+) DCs exhibited a markedly impaired phenotype when compared with WT DCs. They expressed very low levels of costimulatory molecules (intercellular adhesion molecule [ICAM]-1, CD40, CD80, CD86) and of the T cell area-homing chemokine receptor CCR7.

See also

Interactions

IRF8 has been shown to interact with IRF1[4][5] and COPS2.[6]

References

  1. ^ a b "Entrez Gene: IRF8 interferon regulatory factor 8". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3394.  
  2. ^ Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ (December 1992). "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes". J. Biol. Chem. 267 (35): 25589–96. PMID 1460054. http://www.jbc.org/cgi/reprint/267/35/25589.  
  3. ^ Nehyba J, Hrdlicková R, Burnside J, Bose HR (June 2002). "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein". Mol. Cell. Biol. 22 (11): 3942–57. doi:10.1128/MCB.22.11.3942-3957.2002. PMID 11997525.  
  4. ^ Schaper, F; Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi B Z, Hauser H (Oct. 1998). "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. (ENGLAND) 335 ( Pt 1): 147–57. ISSN 0264-6021. PMID 9742224.  
  5. ^ Sharf, R; Azriel A, Lejbkowicz F, Winograd S S, Ehrlich R, Levi B Z (Jun. 1995). "Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors". J. Biol. Chem. (UNITED STATES) 270 (22): 13063–9. ISSN 0021-9258. PMID 7768900.  
  6. ^ Cohen, H; Azriel A, Cohen T, Meraro D, Hashmueli S, Bech-Otschir D, Kraft R, Dubiel W, Levi B Z (Dec. 2000). "Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome". J. Biol. Chem. (UNITED STATES) 275 (50): 39081–9. doi:10.1074/jbc.M004900200. ISSN 0021-9258. PMID 10991940.  

Illustrations

IRF8 in host response.png

Further reading

  • Weisz A, Marx P, Sharf R, et al. (1993). "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes.". J. Biol. Chem. 267 (35): 25589–96. PMID 1460054.  
  • Sharf R, Azriel A, Lejbkowicz F, et al. (1995). "Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors.". J. Biol. Chem. 270 (22): 13063–9. doi:10.1074/jbc.270.22.13063. PMID 7768900.  
  • Holtschke T, Löhler J, Kanno Y, et al. (1996). "Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene.". Cell 87 (2): 307–17. doi:10.1016/S0092-8674(00)81348-3. PMID 8861914.  
  • Schaper F, Kirchhoff S, Posern G, et al. (1998). "Functional domains of interferon regulatory factor I (IRF-1).". Biochem. J. 335 ( Pt 1): 147–57. PMID 9742224.  
  • Li W, Nagineni CN, Ge H, et al. (1999). "Interferon consensus sequence-binding protein is constitutively expressed and differentially regulated in the ocular lens.". J. Biol. Chem. 274 (14): 9686–91. doi:10.1074/jbc.274.14.9686. PMID 10092656.  
  • Li W, Nagineni CN, Hooks JJ, et al. (1999). "Interferon-gamma signaling in human retinal pigment epithelial cells mediated by STAT1, ICSBP, and IRF-1 transcription factors.". Invest. Ophthalmol. Vis. Sci. 40 (5): 976–82. PMID 10102295.  
  • Rehli M, Poltorak A, Schwarzfischer L, et al. (2000). "PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene.". J. Biol. Chem. 275 (13): 9773–81. doi:10.1074/jbc.275.13.9773. PMID 10734131.  
  • Cohen H, Azriel A, Cohen T, et al. (2001). "Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome.". J. Biol. Chem. 275 (50): 39081–9. doi:10.1074/jbc.M004900200. PMID 10991940.  
  • Nehyba J, Hrdlicková R, Burnside J, Bose HR (2002). "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein.". Mol. Cell. Biol. 22 (11): 3942–57. doi:10.1128/MCB.22.11.3942-3957.2002. PMID 11997525.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Zhu C, Saberwal G, Lu Y, et al. (2005). "The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1.". J. Biol. Chem. 279 (49): 50874–85. doi:10.1074/jbc.M405736200. PMID 15371411.  
  • Liu J, Guan X, Tamura T, et al. (2005). "Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein.". J. Biol. Chem. 279 (53): 55609–17. doi:10.1074/jbc.M406565200. PMID 15489234.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.  
  • Barrios-Rodiles M, Brown KR, Ozdamar B, et al. (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells.". Science 307 (5715): 1621–5. doi:10.1126/science.1105776. PMID 15761153.  
  • Xiong H, Li H, Kong HJ, et al. (2005). "Ubiquitin-dependent degradation of interferon regulatory factor-8 mediated by Cbl down-regulates interleukin-12 expression.". J. Biol. Chem. 280 (25): 23531–9. doi:10.1074/jbc.M414296200. PMID 15837792.  
  • Zhao J, Kong HJ, Li H, et al. (2006). "IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways.". J. Biol. Chem. 281 (15): 10073–80. doi:10.1074/jbc.M507788200. PMID 16484229.  
  • Huang W, Saberwal G, Horvath E, et al. (2006). "Leukemia-associated, constitutively active mutants of SHP2 protein tyrosine phosphatase inhibit NF1 transcriptional activation by the interferon consensus sequence binding protein.". Mol. Cell. Biol. 26 (17): 6311–32. doi:10.1128/MCB.00036-06. PMID 16914719.  
  • Dimberg A, Kårehed K, Nilsson K, Oberg F (2006). "Inhibition of monocytic differentiation by phosphorylation-deficient Stat1 is associated with impaired expression of Stat2, ICSBP/IRF8 and C/EBPepsilon.". Scand. J. Immunol. 64 (3): 271–9. doi:10.1111/j.1365-3083.2006.01827.x. PMID 16918696.  
  • Peng YB, Yerle M, Liu B (2007). "Mapping of nine porcine interferon regulatory factor genes.". Anim. Genet. 37 (6): 600–1. doi:10.1111/j.1365-2052.2006.01525.x. PMID 17121613.  
  • Huang W, Horvath E, Eklund EA (2007). "PU.1, interferon regulatory factor (IRF) 2, and the interferon consensus sequence-binding protein (ICSBP/IRF8) cooperate to activate NF1 transcription in differentiating myeloid cells.". J. Biol. Chem. 282 (9): 6629–43. doi:10.1074/jbc.M607760200. PMID 17200120.  
  • Mattei Fabrizio, Schiavoni G, Borghi P, Venditti M, Canini I, Sestili P, Pietraforte I, Morse HC 3rd, Ramoni C, Belardelli F, Gabriele L (2006). "ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells.". Blood 108 (2): 609–617. doi:10.1182/blood-2005-11-4490. PMID 16569763.  
  • Schiavoni Giovanna, Mattei F, Borghi P, Sestili P, Venditti M, Morse HC 3rd, Belardelli F, Gabriele L (2004). "ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells.". Blood 103 (6): 2221–2228. doi:10.1182/blood-2003-09-3007. PMID 14615368.  
  • Schiavoni Giovanna, Mattei F, Sestili P, Borghi P, Venditti M, Morse HC 3rd, Belardelli F, Gabriele L (2002). "ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells.". J. Exp. Med. 196 (11): 1415–1425. doi:10.1084/jem.20021263. PMID 12461077.  

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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