Biology:IRF5

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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 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. 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. 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. 
  3. 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. 
  4. 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. Bibcode2020Natur.581..316H. 
  5. "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. 
  6. "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. 
  7. 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. 
  8. 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. 
  9. 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

External links

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