Biology:IRF1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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:

See also

References

  1. ↑ "Sequence of a cDNA coding for human IRF-1". Nucleic Acids Res 17 (8): 3292. Jun 1989. doi:10.1093/nar/17.8.3292. PMID 2726461. 
  2. ↑ "Assignment of the human interferon regulatory factor-1 (IRF1) gene to chromosome 5q23-q31". Genomics 10 (4): 1097–9. Nov 1991. doi:10.1016/0888-7543(91)90208-V. PMID 1680796. 
  3. ↑ "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. doi:10.1016/S0092-8674(88)91307-4. PMID 3409321. 
  4. ↑ "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation". Nature 391 (6662): 103–6. January 1998. doi:10.1038/34224. PMID 9422515. Bibcode: 1998Natur.391..103E. 
  5. ↑ "Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53". Mol. Cell. Biol. 24 (22): 10083–98. November 2004. doi:10.1128/MCB.24.22.10083-10098.2004. PMID 15509808. 
  6. ↑ "Entrez Gene: IRF1 interferon regulatory factor 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3659. 
  7. ↑ "Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain". J. Biol. Chem. 285 (49): 38348–61. December 2010. doi:10.1074/jbc.M110.149476. PMID 20817723. 
  8. ↑ "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. doi:10.1074/jbc.M110.153122. PMID 20947504. 
  9. ↑ "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. doi:10.1089/jir.2008.0099. PMID 19642896. 
  10. ↑ "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. doi:10.1074/jbc.M109.019505. PMID 19502235. 
  11. ↑ "Functional domains of interferon regulatory factor I (IRF-1)". Biochem. J. 335 (1): 147–57. October 1998. doi:10.1042/bj3350147. PMID 9742224. 
  12. ↑ "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. doi:10.1074/jbc.270.22.13063. PMID 7768900. 
  13. ↑ "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. doi:10.1038/sj.jid.5700716. PMID 17255955. 
  14. ↑ "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. doi:10.1073/pnas.0607181103. PMID 17018642. Bibcode: 2006PNAS..10315136N. 
  15. ↑ "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. doi:10.1128/MCB.19.3.1810. PMID 10022868. 
  16. ↑ "Adenovirus E1A down-regulates LMP2 transcription by interfering with the binding of stat1 to IRF1". J. Biol. Chem. 275 (27): 20406–11. July 2000. doi:10.1074/jbc.M001861200. PMID 10764778. 
  17. ↑ "Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors". J. Exp. Med. 195 (10): 1359–70. May 2002. doi:10.1084/jem.20010753. PMID 12021315. 
  18. ↑ "Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs". Biochim. Biophys. Acta 1783 (9): 1654–62. September 2008. doi:10.1016/j.bbamcr.2008.04.006. PMID 18472010. 
  19. ↑ Gupta, M.; Rath, PC (2014). "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.". Int J Biol Macromol 65: 41–50. doi:10.1016/j.ijbiomac.2014.01.005. PMID 24412152. 

Further reading

External links

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



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