Interferon_Regulatory_Factor_3

IRF3

IRF3

Protein-coding gene in the species Homo sapiens

Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.[5]

Quick Facts Available structures, PDB ...

Function

IRF3 is a member of the interferon regulatory transcription factor (IRF) family.[5] IRF3 was originally discovered as a homolog of IRF1 and IRF2. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites.[6] IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP.[7] The complex translocates into the nucleus for the transcriptional activation of interferons alpha and beta, and further interferon-induced genes.[8]

IRF3 plays an important role in the innate immune system's response to viral infection.[9] Aggregated MAVS have been found to activate IRF3 dimerization.[10] A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons.[11] Another study has shown that IRF3-/- knockouts protect from myocardial infarction.[12] The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-myocardial infarction cardioprotection.[12]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Interactions

IRF3 has been shown to interact with IRF7.[13]

References

  1. [1]
    GRCh38: Ensembl release 89: ENSG00000126456 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000003184 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [5]
    Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R (1999). "Triggering the interferon response: the role of IRF-3 transcription factor". J. Interferon Cytokine Res. 19 (1): 1–13. doi:10.1089/107999099314360. PMID 10048763.
  6. [6]
    Lin R, Heylbroeck C, Genin P, Pitha PM, Hiscott J (Feb 1999). "Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription". Mol Cell Biol. 19 (2): 959–66. doi:10.1128/MCB.19.2.959. PMC 116027. PMID 9891032.
  7. [7]
    Yoneyama M, Suhara W, Fujita T (2002). "Control of IRF-3 activation by phosphorylation". J. Interferon Cytokine Res. 22 (1): 73–6. doi:10.1089/107999002753452674. PMID 11846977.
  8. [8]
    "Entrez Gene: IRF3 interferon regulatory factor 3".
  9. [9]
    Collins SE, Noyce RS, Mossman KL (Feb 2004). "Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication". J Virol. 78 (4): 1706–17. doi:10.1128/JVI.78.4.1706-1717.2004. PMC 369475. PMID 14747536.
  10. [10]
    Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 5, 2011). "MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response". Cell. 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMC 3179916. PMID 21782231.
  11. [11]
    Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, Du F, Ren J, Wu Y, Grishin N, and Chen ZJ (Mar 13, 2015). "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation". Science. 347 (6227): aaa2630. doi:10.1126/science.aaa2630. PMID 25636800.
  12. [12]
    King KR, Aguirre AD, Ye YX, Sun Y, Roh JD, Ng Jr RP, Kohler RH, Arlauckas SP, Iwamoto Y, Savol A, Sadreyev RI, Kelly M, Fitzgibbons TP, Fitzgerald KA, Mitchison T, Libby P, Nahrendorf M, Weissleder R (Nov 6, 2017). "IRF3 and type I interferons fuel a fatal response to myocardial infarction". Nature Medicine. 23 (12): 1481–1487. doi:10.1038/nm.4428. PMC 6477926. PMID 29106401.
  13. [13]
    Au WC, Yeow WS, Pitha PM (Feb 2001). "Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3". Virology. 280 (2): 273–82. doi:10.1006/viro.2000.0782. PMID 11162841.

Further reading

Wikimedia Commons has media related to Interferon regulatory factor 3, IRF-3.
Share this article:

This article uses material from the Wikipedia article Interferon_Regulatory_Factor_3, and is written by contributors. Text is available under a CC BY-SA 4.0 International License; additional terms may apply. Images, videos and audio are available under their respective licenses.