3qu3

Structural highlights

Function

IRF7_MOUSE Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.^{[1] [2] [3] [4]}

See Also

• Interferon regulatory factor

References

1. ↑ Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004 Oct;5(10):1061-8. Epub 2004 Sep 7. PMID:15361868 doi:10.1038/ni1118
2. ↑ Caillaud A, Hovanessian AG, Levy DE, Marie IJ. Regulatory serine residues mediate phosphorylation-dependent and phosphorylation-independent activation of interferon regulatory factor 7. J Biol Chem. 2005 May 6;280(18):17671-7. Epub 2005 Mar 2. PMID:15743772 doi:http://dx.doi.org/10.1074/jbc.M411389200
3. ↑ Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature. 2005 Apr 7;434(7034):772-7. Epub 2005 Mar 30. PMID:15800576 doi:http://dx.doi.org/10.1038/nature03464
4. ↑ Daffis S, Samuel MA, Suthar MS, Keller BC, Gale M Jr, Diamond MS. Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. J Virol. 2008 Sep;82(17):8465-75. doi: 10.1128/JVI.00918-08. Epub 2008 Jun 18. PMID:18562536 doi:http://dx.doi.org/10.1128/JVI.00918-08