IRF1 explained

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]

Interactions

IRF1 has been shown to interact with:

• CHIP^[8]
• GAGE^[9]
• HSP70 / HSP90^[10]
• IRF8^{[11] [12]}
• KPNA2^[13]
• MYD88^[14]
• PCAF^[15]
• STAT1^[16]
• TAT^[17]
• VEGFR2^[18]
• REDD2^[19]

See also

• IRF2
• Interferon regulatory factors

Further reading

• Harada H, Taniguchi T, Tanaka N . The role of interferon regulatory factors in the interferon system and cell growth control . Biochimie . 80 . 8–9 . 641–50 . 1999 . 9865486 . 10.1016/S0300-9084(99)80017-0 .
• Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA . Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth . Biochimie . 80 . 8–9 . 651–8 . 1999 . 9865487 . 10.1016/S0300-9084(99)80018-2 . free .
• Yu-Lee L . Stimulation of interferon regulatory factor-1 by prolactin . Lupus . 10 . 10 . 691–9 . 2002 . 11721695 . 10.1191/096120301717164921 . 13547888 .
• Pine R . IRF and tuberculosis . J. Interferon Cytokine Res. . 22 . 1 . 15–25 . 2002 . 11846972 . 10.1089/107999002753452629 .
• Romeo G, Fiorucci G, Chiantore MV, Percario ZA, Vannucchi S, Affabris E . IRF-1 as a negative regulator of cell proliferation . J. Interferon Cytokine Res. . 22 . 1 . 39–47 . 2002 . 11846974 . 10.1089/107999002753452647 .
• Cha Y, Sims SH, Romine MF, Kaufmann M, Deisseroth AB . Human interferon regulatory factor 1: intron-exon organization . DNA Cell Biol. . 11 . 8 . 605–11 . 1992 . 1382447 . 10.1089/dna.1992.11.605 .
• 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 . 58 . 4 . 729–39 . 1989 . 2475256 . 10.1016/0092-8674(89)90107-4 . 2033941 .
• 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 . 54 . 6 . 903–13 . 1988 . 3409321 . 10.1016/S0092-8674(88)91307-4 . 35063951 .
• Harada H, Takahashi E, Itoh S, Harada K, Hori TA, 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. . 14 . 2 . 1500–9 . 1994 . 7507207 . 358505 . 10.1128/MCB.14.2.1500.
• Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ . Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors . J. Biol. Chem. . 270 . 22 . 13063–9 . 1995 . 7768900 . 10.1074/jbc.270.22.13063 . free .
• Willman CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF . Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia . Science . 259 . 5097 . 968–71 . 1993 . 8438156 . 10.1126/science.8438156 . 1993Sci...259..968W . 40142541 .
• Drew PD, Franzoso G, Becker KG, Bours V, Carlson LM, Siebenlist U, Ozato K . 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 . 1997 . 8746784 . 10.1089/jir.1995.15.1037 .
• Ronco LV, Karpova AY, Vidal M, Howley PM . Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity . Genes Dev. . 12 . 13 . 2061–72 . 1998 . 9649509 . 316980 . 10.1101/gad.12.13.2061 .
• Nozawa H, Oda E, Ueda S, Tamura G, Maesawa C, Muto T, Taniguchi T, Tanaka N . Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer . Int. J. Cancer . 77 . 4 . 522–7 . 1998 . 9679752 . 10.1002/(SICI)1097-0215(19980812)77:4<522::AID-IJC8>3.0.CO;2-W . 25951704 .
• Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H . Functional domains of interferon regulatory factor I (IRF-1) . Biochem. J. . 335 . 1 . 147–57 . 1998 . 9742224 . 1219763 . 10.1042/bj3350147.
• Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K . 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 . 1999 . 10022868 . 83974 . 10.1128/MCB.19.3.1810.

Notes and References

1. Maruyama M, Fujita T, Taniguchi T . Sequence of a cDNA coding for human IRF-1 . Nucleic Acids Res . 17 . 8 . 3292 . Jun 1989 . 2726461 . 317732 . 10.1093/nar/17.8.3292 .
2. Itoh S, Harada H, Nakamura Y, White R, Taniguchi T . Assignment of the human interferon regulatory factor-1 (IRF1) gene to chromosome 5q23-q31 . Genomics . 10 . 4 . 1097–9 . Nov 1991 . 1680796 . 10.1016/0888-7543(91)90208-V .
3. 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 . 54 . 6 . 903–13 . September 1988 . 3409321 . 10.1016/S0092-8674(88)91307-4 . 35063951 .
4. Escalante CR, Yie J, Thanos D, Aggarwal AK . Structure of IRF-1 with bound DNA reveals determinants of interferon regulation . Nature . 391 . 6662 . 103–6 . January 1998 . 9422515 . 10.1038/34224 . 1998Natur.391..103E . 4394514 .
5. Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL . Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 . Mol. Cell. Biol. . 24 . 22 . 10083–98 . November 2004 . 15509808 . 525491 . 10.1128/MCB.24.22.10083-10098.2004 .
6. Web site: Entrez Gene: IRF1 interferon regulatory factor 1.
7. Möller A, Pion E, Narayan V, Ball KL . Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain . J. Biol. Chem. . 285 . 49 . 38348–61 . December 2010 . 20817723 . 2992268 . 10.1074/jbc.M110.149476 . free .
8. Narayan V, Pion E, Landré V, Müller P, Ball KL . Docking dependent ubiquitination of the interferon regulatory factor-1 tumour suppressor protein by the ubiquitin ligase CHIP . J Biol Chem . 286 . 1 . 607–19 . October 2010 . 20947504 . 3013021 . 10.1074/jbc.M110.153122 . free .
9. Kular RK, Yehiely F, Kotlo KU, Cilensek ZM, Bedi R, Deiss LP . 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 . October 2009 . 19642896 . 10.1089/jir.2008.0099 .
10. Narayan V, Eckert M, Zylicz A, Zylicz M, Ball KL . 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 . September 2009 . 19502235 . 2757990 . 10.1074/jbc.M109.019505 . free .
11. Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H . Functional domains of interferon regulatory factor I (IRF-1) . Biochem. J. . 335 . 1 . 147–57 . October 1998 . 9742224 . 1219763 . 10.1042/bj3350147.
12. Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ . Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors . J. Biol. Chem. . 270 . 22 . 13063–9 . June 1995 . 7768900 . 10.1074/jbc.270.22.13063 . free .
13. Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K, Katayama I, Kaneda Y . 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 . June 2007 . 17255955 . 10.1038/sj.jid.5700716 . free .
14. Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K . 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 . October 2006 . 17018642 . 1586247 . 10.1073/pnas.0607181103 . 2006PNAS..10315136N . free .
15. Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K . 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 . March 1999 . 10022868 . 83974 . 10.1128/MCB.19.3.1810.
16. Chatterjee-Kishore M, van Den Akker F, Stark GR . Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1 . J. Biol. Chem. . 275 . 27 . 20406–11 . July 2000 . 10764778 . 10.1074/jbc.M001861200 . free .
17. Sgarbanti M, Borsetti A, Moscufo N, Bellocchi MC, Ridolfi B, Nappi F, Marsili G, Marziali G, Coccia EM, Ensoli B, Battistini A . Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors . J. Exp. Med. . 195 . 10 . 1359–70 . May 2002 . 12021315 . 2193759 . 10.1084/jem.20010753 .
18. Lee JH, Chun T, Park SY, Rho SB . Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs . Biochim. Biophys. Acta . 1783 . 9 . 1654–62 . September 2008 . 18472010 . 10.1016/j.bbamcr.2008.04.006 . free .
19. Gupta M, Rath PC . Interferon regulatory factor-1 (IRF-1) interacts with regulated in development and DNA damage response 2 (REDD2) in the cytoplasm of mouse bone marrow cells . International Journal of Biological Macromolecules . 65 . 41–50 . April 2014 . 24412152 . 10.1016/j.ijbiomac.2014.01.005 .