IRF1

Interferon regulatory factor 1
PDB rendering based on 1if1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1if1​
Identifiers
Symbols	IRF1 ; IRF-1; MAR
External IDs	OMIM: 147575 MGI: 96590 HomoloGene: 1658 GeneCards: IRF1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • protein binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • cytoplasm • cytosol Biological process • regulation of adaptive immune response • transcription from RNA polymerase II promoter • apoptotic process • cell cycle arrest • blood coagulation • negative regulation of cell proliferation • cytokine-mediated signaling pathway • positive regulation of type I interferon production • positive regulation of interferon-beta production • regulation of MyD88-dependent toll-like receptor signaling pathway • cellular response to interferon-beta • CD8-positive, alpha-beta T cell differentiation • positive regulation of interleukin-12 biosynthetic process • regulation of innate immune response • negative regulation of regulatory T cell differentiation • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • defense response to virus • regulation of cell cycle • interferon-gamma-mediated signaling pathway • type I interferon signaling pathway • cellular response to mechanical stimulus • regulation of CD8-positive, alpha-beta T cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3659	16362
Ensembl	ENSG00000125347	ENSMUSG00000018899
UniProt	P10914	P15314
RefSeq (mRNA)	NM_002198	NM_001159393
RefSeq (protein)	NP_002189	NP_001152865
Location (UCSC)	Chr 5: 132.48 – 132.49 Mb	Chr 11: 53.77 – 53.78 Mb
PubMed search

Interferon regulatory factor 1 is a protein that in humans is encoded by the IRF1 gene.^[1][2]

Function

Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially described as a transcription factor able to activate expression of the cytokine Interferon beta,^[3] IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes. IRF-1 regulates expression of target genes by binding to an interferon stimulated response element (ISRE) in their promoters. The IRF-1 protein binds to the ISRE via an N-terminal helix-turn-helix DNA binding domain,^[4] which is highly conserved among all IRF proteins.

Beyond its function as a transcription factor, IRF-1 has also been shown to trans-activate the tumour suppressor protein p53 through the recruitment of its co-factor p300.^[5]

IRF-1 has been shown to play roles in the immune response, regulating apoptosis, DNA damage and tumor suppression.^[6]

Regulation

It has been shown that the extreme C-terminus of IRF-1 regulates its ability to activate transcription, nanobodies targeting this domain (MF1) are able to increase IRF-1 activity.^[7]

Model organisms

Irf1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Abnormal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Citrobacter infection	Normal[8]
All tests and analysis from[9][10]

Model organisms have been used in the study of IRF1 function. A conditional knockout mouse line, called Irf1^{tm1a(EUCOMM)Wtsi[11][12]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[9][16] Twenty five tests were carried out and two phenotypes were reported. Homozygous mutant animals had abnormal peripheral blood lymphocytes, specifically decreased CD8-positive T cell and NK cell numbers and an increase in CD4-positive T cells. The mice also had an abnormal integument phenotype determined by a study of tail epidermis.^[9]

Interactions

IRF1 has been shown to interact with:

• CHIP^[17]
• GAGE^[18]
• HSP70 / HSP90^[19]
• IRF8^[20][21]
• KPNA2^[22]
• MYD88^[23]
• PCAF^[24]
• STAT1^[25]
• TAT^[26]
• VEGFR2^[27]

See also

• IRF2
• Interferon regulatory factors

References

1. Maruyama M, Fujita T, Taniguchi T (Jun 1989). "Sequence of a cDNA coding for human IRF-1". Nucleic Acids Res 17 (8): 3292. doi:10.1093/nar/17.8.3292. PMC 317732. PMID 2726461.
2. Itoh S, Harada H, Nakamura Y, White R, Taniguchi T (Nov 1991). "Assignment of the human interferon regulatory factor-1 (IRF1) gene to chromosome 5q23-q31". Genomics 10 (4): 1097–9. doi:10.1016/0888-7543(91)90208-V. PMID 1680796.
3. Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T (September 1988). "Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements". Cell 54 (6): 903–13. doi:10.1016/S0092-8674(88)91307-4. PMID 3409321.
4. Escalante CR, Yie J, Thanos D, Aggarwal AK (January 1998). "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation". Nature 391 (6662): 103–6. doi:10.1038/34224. PMID 9422515.
5. Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL (November 2004). "Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53". Mol. Cell. Biol. 24 (22): 10083–98. doi:10.1128/MCB.24.22.10083-10098.2004. PMC 525491. PMID 15509808.
6. "Entrez Gene: IRF1 interferon regulatory factor 1".
7. Möller A, Pion E, Narayan V, Ball KL (December 2010). "Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain". J. Biol. Chem. 285 (49): 38348–61. doi:10.1074/jbc.M110.149476. PMC 2992268. PMID 20817723.
8. "Citrobacter infection data for Irf1". Wellcome Trust Sanger Institute.
9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
10. Mouse Resources Portal, Wellcome Trust Sanger Institute.
11. "International Knockout Mouse Consortium".
12. "Mouse Genome Informatics".
13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
14. Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
15. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
16. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
17. Narayan V, Pion E, Landré V, Müller P, Ball KL (October 2010). "Docking dependent ubiquitination of the interferon regulatory factor-1 tumour suppressor protein by the ubiquitin ligase CHIP". J Biol Chem. 286 (1): 607–19. doi:10.1074/jbc.M110.153122. PMC 3013021. PMID 20947504.
18. Kular RK, Yehiely F, Kotlo KU, Cilensek ZM, Bedi R, Deiss LP (October 2009). "GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1". J. Interferon Cytokine Res. 29 (10): 645–55. doi:10.1089/jir.2008.0099. PMID 19642896.
19. Narayan V, Eckert M, Zylicz A, Zylicz M, Ball KL (September 2009). "Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery". J Biol Chem. 284 (38): 25889–99. doi:10.1074/jbc.M109.019505. PMC 2757990. PMID 19502235.
20. Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H (October 1998). "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. 335 (1): 147–57. PMC 1219763. PMID 9742224.
21. Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ (June 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.
22. Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K, Katayama I, Kaneda Y (June 2007). "Differential regulation of karyopherin alpha 2 expression by TGF-beta1 and IFN-gamma in normal human epidermal keratinocytes: evident contribution of KPNA2 for nuclear translocation of IRF-1". J. Invest. Dermatol. 127 (6): 1456–64. doi:10.1038/sj.jid.5700716. PMID 17255955.
23. Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K (October 2006). "Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program". Proc. Natl. Acad. Sci. U.S.A. 103 (41): 15136–41. doi:10.1073/pnas.0607181103. PMC 1586247. PMID 17018642.
24. Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K (March 1999). "The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness". Mol. Cell. Biol. 19 (3): 1810–20. PMC 83974. PMID 10022868.
25. Chatterjee-Kishore M, van Den Akker F, Stark GR (July 2000). "Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1". J. Biol. Chem. 275 (27): 20406–11. doi:10.1074/jbc.M001861200. PMID 10764778.
26. Sgarbanti M, Borsetti A, Moscufo N, Bellocchi MC, Ridolfi B, Nappi F, Marsili G, Marziali G, Coccia EM, Ensoli B, Battistini A (May 2002). "Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors". J. Exp. Med. 195 (10): 1359–70. doi:10.1084/jem.20010753. PMC 2193759. PMID 12021315.
27. Lee JH, Chun T, Park SY, Rho SB (September 2008). "Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs". Biochim. Biophys. Acta 1783 (9): 1654–62. doi:10.1016/j.bbamcr.2008.04.006. PMID 18472010.

Further reading

• Harada H, Taniguchi T, Tanaka N (1999). "The role of interferon regulatory factors in the interferon system and cell growth control". Biochimie 80 (8–9): 641–50. doi:10.1016/S0300-9084(99)80017-0. PMID 9865486.
• Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA (1999). "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie 80 (8–9): 651–8. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487.
• Yu-Lee L (2002). "Stimulation of interferon regulatory factor-1 by prolactin". Lupus 10 (10): 691–9. doi:10.1191/096120301717164921. PMID 11721695.
• Pine R (2002). "IRF and tuberculosis". J. Interferon Cytokine Res. 22 (1): 15–25. doi:10.1089/107999002753452629. PMID 11846972.
• Romeo G, Fiorucci G, Chiantore MV, Percario ZA, Vannucchi S, Affabris E (2002). "IRF-1 as a negative regulator of cell proliferation". J. Interferon Cytokine Res. 22 (1): 39–47. doi:10.1089/107999002753452647. PMID 11846974.
• Cha Y, Sims SH, Romine MF, Kaufmann M, Deisseroth AB (1992). "Human interferon regulatory factor 1: intron-exon organization". DNA Cell Biol. 11 (8): 605–11. doi:10.1089/dna.1992.11.605. PMID 1382447.
• Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T, Taniguchi T (1989). "Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes". Cell 58 (4): 729–39. doi:10.1016/0092-8674(89)90107-4. PMID 2475256.
• Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T (1988). "Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements". Cell 54 (6): 903–13. doi:10.1016/S0092-8674(88)91307-4. PMID 3409321.
• Harada H, Takahashi E, Itoh S, Harada K, Hori TA, Taniguchi T (1994). "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. 14 (2): 1500–9. PMC 358505. PMID 7507207.
• Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ (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.
• Willman CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF (1993). "Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia". Science 259 (5097): 968–71. doi:10.1126/science.8438156. PMID 8438156.
• Drew PD, Franzoso G, Becker KG, Bours V, Carlson LM, Siebenlist U, Ozato K (1997). "NF kappa B and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression". J. Interferon Cytokine Res. 15 (12): 1037–45. doi:10.1089/jir.1995.15.1037. PMID 8746784.
• Ronco LV, Karpova AY, Vidal M, Howley PM (1998). "Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity". Genes Dev. 12 (13): 2061–72. doi:10.1101/gad.12.13.2061. PMC 316980. PMID 9649509.
• Nozawa H, Oda E, Ueda S, Tamura G, Maesawa C, Muto T, Taniguchi T, Tanaka N (1998). "Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer". Int. J. Cancer 77 (4): 522–7. doi:10.1002/(SICI)1097-0215(19980812)77:4<522::AID-IJC8>3.0.CO;2-W. PMID 9679752.
• Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H (1998). "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. 335 (1): 147–57. PMC 1219763. PMID 9742224.
• Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K (1999). "The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness". Mol. Cell. Biol. 19 (3): 1810–20. PMC 83974. PMID 10022868.

External links

• IRF1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook IRF1

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