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]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^
abHiscott 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.
PMID10048763.
^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.
PMID11846977.
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.
PMID11846977.
Lowther WJ, Moore PA, Carter KC, Pitha PM (1999). "Cloning and functional analysis of the human IRF-3 promoter". DNA Cell Biol. 18 (9): 685–92.
doi:
10.1089/104454999314962.
PMID10492399.
Suhara W, Yoneyama M, Iwamura T, Yoshimura S, Tamura K, Namiki H, Aimoto S, Fujita T (2000). "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300". J. Biochem. 128 (2): 301–7.
doi:
10.1093/oxfordjournals.jbchem.a022753.
PMID10920266.
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]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^
abHiscott 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.
PMID10048763.
^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.
PMID11846977.
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.
PMID11846977.
Lowther WJ, Moore PA, Carter KC, Pitha PM (1999). "Cloning and functional analysis of the human IRF-3 promoter". DNA Cell Biol. 18 (9): 685–92.
doi:
10.1089/104454999314962.
PMID10492399.
Suhara W, Yoneyama M, Iwamura T, Yoshimura S, Tamura K, Namiki H, Aimoto S, Fujita T (2000). "Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300". J. Biochem. 128 (2): 301–7.
doi:
10.1093/oxfordjournals.jbchem.a022753.
PMID10920266.