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/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3663.
- ↑ 2.0 2.1 "The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family". Cold Spring Harbor Perspectives in Biology 10 (11). November 2018. doi:10.1101/cshperspect.a028423. PMID 28963109.
- ↑ "The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2". Immunobiology 223 (1): 101–111. January 2018. doi:10.1016/j.imbio.2017.10.005. PMID 29032836.
- ↑ "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9". Nature 581 (7808): 316–322. May 2020. 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). March 2015. doi:10.1126/science.aaa2630. PMID 25636800.
- ↑ "IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses". Nature Immunology 12 (3): 231–238. March 2011. doi:10.1038/ni.1990. PMID 21240265. https://hal.science/hal-00608917.
- ↑ "On the role of IRF in host defense". Journal of Interferon & Cytokine Research 22 (1): 59–71. January 2002. doi:10.1089/107999002753452665. PMID 11846976.
- ↑ ""Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway" (in English). Frontiers in Oncology 8. 2018. doi:10.3389/fonc.2018.00287. PMID 30109213.
- ↑ "The Molecular Basis of Viral Inhibition of IRF- and STAT-Dependent Immune Responses" (in English). Frontiers in Immunology 9. 2019. doi:10.3389/fimmu.2018.03086. PMID 30671058.
Further reading
- "Role of the interferon regulatory factors (IRFs) in virus-mediated signaling and regulation of cell growth". Biochimie 80 (8–9): 651–658. 1999. doi:10.1016/S0300-9084(99)80018-2. PMID 9865487.
- "On the role of IRF in host defense". Journal of Interferon & Cytokine Research 22 (1): 59–71. January 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". The Journal of Biological Chemistry 276 (26): 23382–23390. June 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". Molecular and Cellular Biology 22 (11): 3942–3957. June 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". Molecular and Cellular Biology 22 (16): 5721–5740. August 2002. doi:10.1128/MCB.22.16.5721-5740.2002. PMID 12138184.
- "Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes". The Journal of Biological Chemistry 278 (19): 16630–16641. May 2003. doi:10.1074/jbc.M212609200. PMID 12600985.
- "Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death". Cancer Research 63 (19): 6424–6431. October 2003. PMID 14559832.
- "Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection". The Journal of Biological Chemistry 279 (43): 45194–45207. October 2004. doi:10.1074/jbc.M400726200. PMID 15308637.
- "A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization". The Journal of Biological Chemistry 280 (4): 3088–3095. January 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". American Journal of Human Genetics 76 (3): 528–537. March 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): 243–249. March 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". The Journal of Biological Chemistry 280 (17): 17005–17012. April 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". The Journal of Biological Chemistry 280 (22): 21078–21090. June 2005. doi:10.1074/jbc.M500543200. PMID 15805103.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. October 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". Nature Genetics 38 (5): 550–555. May 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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