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Irf1

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Irf1

Interferon regulatory factor 1

PDB rendering based on 1if1.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; IRF-1; MAR
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
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

knockout mouse line, called Irf1tm1a(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]

See also

Interactions

IRF1 has been shown to interact with:

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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  8. ^ infection data for Irf1"Citrobacter". Wellcome Trust Sanger Institute. 
  9. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248).  
  10. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ^ "International Knockout Mouse Consortium". 
  12. ^ "Mouse Genome Informatics". 
  13. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342.  
  14. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3.  
  15. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13.  
  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.  
  17. ^ Narayan V, Pion E, Landre V, Muller 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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  

Further reading

External links

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