IRF1

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,{{cite journal | vauthors = Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T | title = Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements | journal = Cell | volume = 54 | issue = 6 | pages = 903–13 | date = September 1988 | pmid = 3409321 | doi = 10.1016/S0092-8674(88)91307-4 | s2cid = 35063951 }} 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,{{cite journal | vauthors = Escalante CR, Yie J, Thanos D, Aggarwal AK | title = Structure of IRF-1 with bound DNA reveals determinants of interferon regulation | journal = Nature | volume = 391 | issue = 6662 | pages = 103–6 | date = January 1998 | pmid = 9422515 | doi = 10.1038/34224 | bibcode = 1998Natur.391..103E | s2cid = 4394514 }} 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.{{cite journal | vauthors = Dornan D, Eckert M, Wallace M, Shimizu H, Ramsay E, Hupp TR, Ball KL | title = Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 | journal = Mol. Cell. Biol. | volume = 24 | issue = 22 | pages = 10083–98 | date = November 2004 | pmid = 15509808 | pmc = 525491 | doi = 10.1128/MCB.24.22.10083-10098.2004 }}

IRF-1 has been shown to play roles in the immune response, regulating apoptosis, DNA damage and tumor suppression.{{cite web | title = Entrez Gene: IRF1 interferon regulatory factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3659}}

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.{{cite journal | vauthors = Möller A, Pion E, Narayan V, Ball KL | title = Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain | journal = J. Biol. Chem. | volume = 285 | issue = 49 | pages = 38348–61 | date = December 2010 | pmid = 20817723 | pmc = 2992268 | doi = 10.1074/jbc.M110.149476 | doi-access = free }}

IRF1 has been shown to interact with:

• CHIP{{cite journal | vauthors = Narayan V, Pion E, Landré V, Müller P, Ball KL | title = Docking dependent ubiquitination of the interferon regulatory factor-1 tumour suppressor protein by the ubiquitin ligase CHIP | journal = J Biol Chem | volume = 286 | issue = 1 | pages = 607–19 | date = October 2010 | pmid = 20947504 | pmc = 3013021 | doi = 10.1074/jbc.M110.153122 | doi-access = free }}
• GAGE{{cite journal | vauthors = Kular RK, Yehiely F, Kotlo KU, Cilensek ZM, Bedi R, Deiss LP | title = GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1 | journal = J. Interferon Cytokine Res. | volume = 29 | issue = 10 | pages = 645–55 | date = October 2009 | pmid = 19642896 | doi = 10.1089/jir.2008.0099 }}
• HSP70 / HSP90{{cite journal | vauthors = Narayan V, Eckert M, Zylicz A, Zylicz M, Ball KL | title = Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery | journal = J Biol Chem | volume = 284 | issue = 38 | pages = 25889–99 | date = September 2009 | pmid = 19502235 | pmc = 2757990 | doi = 10.1074/jbc.M109.019505 | doi-access = free }}
• IRF8{{cite journal | vauthors = Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H | title = Functional domains of interferon regulatory factor I (IRF-1) | journal = Biochem. J. | volume = 335 | issue = 1 | pages = 147–57 | date = October 1998 | pmid = 9742224 | pmc = 1219763 | doi = 10.1042/bj3350147}}{{cite journal | vauthors = Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ | title = Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors | journal = J. Biol. Chem. | volume = 270 | issue = 22 | pages = 13063–9 | date = June 1995 | pmid = 7768900 | doi = 10.1074/jbc.270.22.13063 | doi-access = free }}
• KPNA2{{cite journal | vauthors = Umegaki N, Tamai K, Nakano H, Moritsugu R, Yamazaki T, Hanada K, Katayama I, Kaneda Y | title = 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 | journal = J. Invest. Dermatol. | volume = 127 | issue = 6 | pages = 1456–64 | date = June 2007 | pmid = 17255955 | doi = 10.1038/sj.jid.5700716 | doi-access = free }}
• MYD88{{cite journal | vauthors = Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K | title = Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 103 | issue = 41 | pages = 15136–41 | date = October 2006 | pmid = 17018642 | pmc = 1586247 | doi = 10.1073/pnas.0607181103 | bibcode = 2006PNAS..10315136N | doi-access = free }}
• PCAF{{cite journal | vauthors = Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K | title = The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness | journal = Mol. Cell. Biol. | volume = 19 | issue = 3 | pages = 1810–20 | date = March 1999 | pmid = 10022868 | pmc = 83974 | doi = 10.1128/MCB.19.3.1810}}
• STAT1{{cite journal | vauthors = Chatterjee-Kishore M, van Den Akker F, Stark GR | title = Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1 | journal = J. Biol. Chem. | volume = 275 | issue = 27 | pages = 20406–11 | date = July 2000 | pmid = 10764778 | doi = 10.1074/jbc.M001861200 | doi-access = free }}
• TAT{{cite journal | vauthors = Sgarbanti M, Borsetti A, Moscufo N, Bellocchi MC, Ridolfi B, Nappi F, Marsili G, Marziali G, Coccia EM, Ensoli B, Battistini A | title = Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors | journal = J. Exp. Med. | volume = 195 | issue = 10 | pages = 1359–70 | date = May 2002 | pmid = 12021315 | pmc = 2193759 | doi = 10.1084/jem.20010753 }}
• VEGFR2{{cite journal | vauthors = Lee JH, Chun T, Park SY, Rho SB | title = Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs | journal = Biochim. Biophys. Acta | volume = 1783 | issue = 9 | pages = 1654–62 | date = September 2008 | pmid = 18472010 | doi = 10.1016/j.bbamcr.2008.04.006 | doi-access = free }}
• REDD2{{cite journal | vauthors = Gupta M, Rath PC | title = 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 | journal = International Journal of Biological Macromolecules | volume = 65 | pages = 41–50 | date = April 2014 | pmid = 24412152 | doi = 10.1016/j.ijbiomac.2014.01.005 }}

• IRF2
• Interferon regulatory factors

{{reflist}}

{{refbegin|30em}}

• {{cite journal | vauthors = Harada H, Taniguchi T, Tanaka N | title = The role of interferon regulatory factors in the interferon system and cell growth control | journal = Biochimie | volume = 80 | issue = 8–9 | pages = 641–50 | year = 1999 | pmid = 9865486 | doi = 10.1016/S0300-9084(99)80017-0 }}
• {{cite journal | vauthors = Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA | title = Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth | journal = Biochimie | volume = 80 | issue = 8–9 | pages = 651–8 | year = 1999 | pmid = 9865487 | doi = 10.1016/S0300-9084(99)80018-2 | doi-access = free }}
• {{cite journal | vauthors = Yu-Lee L | title = Stimulation of interferon regulatory factor-1 by prolactin | journal = Lupus | volume = 10 | issue = 10 | pages = 691–9 | year = 2002 | pmid = 11721695 | doi = 10.1191/096120301717164921 | s2cid = 13547888 }}
• {{cite journal | vauthors = Pine R | title = IRF and tuberculosis | journal = J. Interferon Cytokine Res. | volume = 22 | issue = 1 | pages = 15–25 | year = 2002 | pmid = 11846972 | doi = 10.1089/107999002753452629 }}
• {{cite journal | vauthors = Romeo G, Fiorucci G, Chiantore MV, Percario ZA, Vannucchi S, Affabris E | title = IRF-1 as a negative regulator of cell proliferation | journal = J. Interferon Cytokine Res. | volume = 22 | issue = 1 | pages = 39–47 | year = 2002 | pmid = 11846974 | doi = 10.1089/107999002753452647 }}
• {{cite journal | vauthors = Cha Y, Sims SH, Romine MF, Kaufmann M, Deisseroth AB | title = Human interferon regulatory factor 1: intron-exon organization | journal = DNA Cell Biol. | volume = 11 | issue = 8 | pages = 605–11 | year = 1992 | pmid = 1382447 | doi = 10.1089/dna.1992.11.605 }}
• {{cite journal | vauthors = Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T, Taniguchi T | title = Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes | journal = Cell | volume = 58 | issue = 4 | pages = 729–39 | year = 1989 | pmid = 2475256 | doi = 10.1016/0092-8674(89)90107-4 | s2cid = 2033941 }}
• {{cite journal | vauthors = Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T | title = Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements | journal = Cell | volume = 54 | issue = 6 | pages = 903–13 | year = 1988 | pmid = 3409321 | doi = 10.1016/S0092-8674(88)91307-4 | s2cid = 35063951 }}
• {{cite journal | vauthors = Harada H, Takahashi E, Itoh S, Harada K, Hori TA, Taniguchi T | title = 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 | journal = Mol. Cell. Biol. | volume = 14 | issue = 2 | pages = 1500–9 | year = 1994 | pmid = 7507207 | pmc = 358505 | doi = 10.1128/MCB.14.2.1500}}
• {{cite journal | vauthors = Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R, Levi BZ | title = Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors | journal = J. Biol. Chem. | volume = 270 | issue = 22 | pages = 13063–9 | year = 1995 | pmid = 7768900 | doi = 10.1074/jbc.270.22.13063 | doi-access = free }}
• {{cite journal | vauthors = Willman CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF | title = Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia | journal = Science | volume = 259 | issue = 5097 | pages = 968–71 | year = 1993 | pmid = 8438156 | doi = 10.1126/science.8438156 | bibcode = 1993Sci...259..968W | s2cid = 40142541 }}
• {{cite journal | vauthors = Drew PD, Franzoso G, Becker KG, Bours V, Carlson LM, Siebenlist U, Ozato K | title = NF kappa B and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression | journal = J. Interferon Cytokine Res. | volume = 15 | issue = 12 | pages = 1037–45 | year = 1997 | pmid = 8746784 | doi = 10.1089/jir.1995.15.1037 }}
• {{cite journal | vauthors = Ronco LV, Karpova AY, Vidal M, Howley PM | title = Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity | journal = Genes Dev. | volume = 12 | issue = 13 | pages = 2061–72 | year = 1998 | pmid = 9649509 | pmc = 316980 | doi = 10.1101/gad.12.13.2061 }}
• {{cite journal | vauthors = Nozawa H, Oda E, Ueda S, Tamura G, Maesawa C, Muto T, Taniguchi T, Tanaka N | title = Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer | journal = Int. J. Cancer | volume = 77 | issue = 4 | pages = 522–7 | year = 1998 | pmid = 9679752 | doi = 10.1002/(SICI)1097-0215(19980812)77:4<522::AID-IJC8>3.0.CO;2-W | s2cid = 25951704 }}
• {{cite journal | vauthors = Schaper F, Kirchhoff S, Posern G, Köster M, Oumard A, Sharf R, Levi BZ, Hauser H | title = Functional domains of interferon regulatory factor I (IRF-1) | journal = Biochem. J. | volume = 335 | issue = 1 | pages = 147–57 | year = 1998 | pmid = 9742224 | pmc = 1219763 | doi = 10.1042/bj3350147}}
• {{cite journal | vauthors = Masumi A, Wang IM, Lefebvre B, Yang XJ, Nakatani Y, Ozato K | title = The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness | journal = Mol. Cell. Biol. | volume = 19 | issue = 3 | pages = 1810–20 | year = 1999 | pmid = 10022868 | pmc = 83974 | doi = 10.1128/MCB.19.3.1810}}

{{refend}}

{{Commons category|Interferon regulatory factor 1 (IRF-1)}}

• {{MeshName|IRF1+protein,+human}}
• {{FactorBook|IRF1}}

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{{Transcription factors|g3}}

{{JAK-STAT signaling pathway}}

Category:Transcription factors

Category:Genes mutated in mice