Biology:IRF5
 Generic protein structure example |
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene.[1] The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.[2]
Function
IRF5 is a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative splice variants encoding different isoforms exist.[1] The regulatory and repression regions of the IRF family are mainly located in the C-terminal of the IRF.[3]
A 2020 study showed that an adaptor protein named TASL play an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif,[4] drawing a similar analogy to the IRF3 activation pathway through the adaptor proteins MAVS, STING and TRIF.[5]
Clinical significance
IRF5 acts as a molecular switch that controls whether macrophages will promote or inhibit inflammation. Blocking the production of IRF5 in macrophages may help treat a wide range of autoimmune diseases, and that boosting IRF5 levels might help treat people whose immune systems are weak, compromised, or damaged. IRF5 seems to work "either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on."[6]
Signaling
The IRF family regulates the gene expression for the interferon (IFN) response to viral infections.[2] IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation.[7] The IRF family can also initiate the JAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK.[8] IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals.[9]
See also
References
- ↑ 1.0 1.1 "Entrez Gene: IRF5 interferon regulatory factor 5". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3663.
- ↑ 2.0 2.1 Negishi, Hideo; Taniguchi, Tadatsugu; Yanai, Hideyuki (2018-11-01). "The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family" (in en). Cold Spring Harbor Perspectives in Biology 10 (11): a028423. doi:10.1101/cshperspect.a028423. ISSN 1943-0264. PMID 28963109.
- ↑ Chistiakov, Dimitry A.; Myasoedova, Veronika A.; Revin, Victor V.; Orekhov, Alexander N.; Bobryshev, Yuri V. (2018-01-01). "The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2" (in en). Immunobiology 223 (1): 101–111. doi:10.1016/j.imbio.2017.10.005. ISSN 0171-2985. PMID 29032836. https://www.sciencedirect.com/science/article/pii/S0171298517301407.
- ↑ Heinz, Leonhard X.; Lee, JangEun; Kapoor, Utkarsh; Kartnig, Felix; Sedlyarov, Vitaly; Papakostas, Konstantinos; César-Razquin, Adrian; Essletzbichler, Patrick et al. (13 May 2020). "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7–9". Nature 581 (7808): 316–322. doi:10.1038/s41586-020-2282-0. PMID 32433612. Bibcode: 2020Natur.581..316H.
- ↑ "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation.". Science 347 (6227): aaa2630. Mar 13, 2015. doi:10.1126/science.aaa2630. PMID 25636800.
- ↑ "IRF5 promotes inflammatory macrophage polarization and T(H)1-T(H)17 responses". Nat Immunol 12 (3): 231–238. January 2011. doi:10.1038/ni.1990. PMID 21240265.
- ↑ Barnes, Betsy; Lubyova, Barbora; Pitha, Paula M. (January 2002). "Review: On the Role of IRF in Host Defense". Journal of Interferon & Cytokine Research 22 (1): 59–71. doi:10.1089/107999002753452665. ISSN 1079-9907. PMID 11846976. https://www.liebertpub.com/doi/pdf/10.1089/107999002753452665.
- ↑ Bousoik, Emira; Montazeri Aliabadi, Hamidreza (2018). ""Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway" (in English). Frontiers in Oncology 8: 287. doi:10.3389/fonc.2018.00287. ISSN 2234-943X. PMID 30109213.
- ↑ Chiang, Hao-Sen; Liu, Helene Minyi (2019). "The Molecular Basis of Viral Inhibition of IRF- and STAT-Dependent Immune Responses" (in English). Frontiers in Immunology 9: 3086. doi:10.3389/fimmu.2018.03086. ISSN 1664-3224. PMID 30671058.
Further reading
- "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie 80 (8–9): 651–8. 1999. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487.
- "On the role of IRF in host defense". J. Interferon Cytokine Res. 22 (1): 59–71. 2002. doi:10.1089/107999002753452665. PMID 11846976.
- "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes". J. Biol. Chem. 276 (26): 23382–90. 2001. doi:10.1074/jbc.M101216200. PMID 11303025.
- "A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein". Mol. Cell. Biol. 22 (11): 3942–57. 2002. doi:10.1128/MCB.22.11.3942-3957.2002. PMID 11997525.
- "Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes". Mol. Cell. Biol. 22 (16): 5721–40. 2002. doi:10.1128/MCB.22.16.5721-5740.2002. PMID 12138184.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes". J. Biol. Chem. 278 (19): 16630–41. 2003. doi:10.1074/jbc.M212609200. PMID 12600985.
- "Human chromosome 7: DNA sequence and biology". Science 300 (5620): 767–72. 2003. doi:10.1126/science.1083423. PMID 12690205. Bibcode: 2003Sci...300..767S.
- "Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death". Cancer Res. 63 (19): 6424–31. 2003. PMID 14559832.
- "Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection". J. Biol. Chem. 279 (43): 45194–207. 2004. doi:10.1074/jbc.M400726200. PMID 15308637.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization". J. Biol. Chem. 280 (4): 3088–95. 2005. doi:10.1074/jbc.M408452200. PMID 15556946.
- "Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus". Am. J. Hum. Genet. 76 (3): 528–37. 2005. doi:10.1086/428480. PMID 15657875.
- "Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors". Nature 434 (7030): 243–9. 2005. doi:10.1038/nature03308. PMID 15665823. Bibcode: 2005Natur.434..243T.
- "The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling". J. Biol. Chem. 280 (17): 17005–12. 2005. doi:10.1074/jbc.M412584200. PMID 15695821.
- "Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function". J. Biol. Chem. 280 (22): 21078–90. June 2005. doi:10.1074/jbc.M500543200. PMID 15805103.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus". Nat. Genet. 38 (5): 550–5. 2006. doi:10.1038/ng1782. PMID 16642019.
External links
- IRF5+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: Q13568 (Interferon regulatory factor 5) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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