Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300
- PMID: 10920266
- DOI: 10.1093/oxfordjournals.jbchem.a022753
Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300
Abstract
Cellular genes including the type I interferon genes are activated in response to viral infection. We previously reported that IRF-3 (interferon regulatory factor 3) is specifically phosphorylated on serine residues and directly transmits a virus-induced signal from the cytoplasm to the nucleus, and then participates in the primary phase of gene induction. In this study, we analyzed the molecular mechanism of IRF-3 activation further. The formation of a stable homomeric complex of IRF-3 between the specifically phosphorylated IRF-3 molecules occurred. While virus-induced IRF-7 did not bind to p300, the phosphorylated IRF-3 complex formed a stable multimeric complex with p300 (active holocomplex). Competition using a synthetic phosphopeptide corresponding to the activated IRF-3 demonstrated that p300 directly recognizes the structure in the vicinity of the phosphorylated residues of IRF-3. These results indicated that the phosphorylation of serine residues at positions 385 and 386 is critical for the formation of the holocomplex, presumably through a conformational switch facilitating homodimer formation and the generation of the interaction interface with CBP/p300.
Similar articles
-
Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3.Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9837-42. doi: 10.1073/pnas.95.17.9837. Proc Natl Acad Sci U S A. 1998. PMID: 9707562 Free PMC article.
-
Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1.Mol Cell Biol. 1998 Mar;18(3):1359-68. doi: 10.1128/MCB.18.3.1359. Mol Cell Biol. 1998. PMID: 9488451 Free PMC article.
-
Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300.EMBO J. 1998 Feb 16;17(4):1087-95. doi: 10.1093/emboj/17.4.1087. EMBO J. 1998. PMID: 9463386 Free PMC article.
-
Control of IRF-3 activation by phosphorylation.J Interferon Cytokine Res. 2002 Jan;22(1):73-6. doi: 10.1089/107999002753452674. J Interferon Cytokine Res. 2002. PMID: 11846977 Review.
-
Triggering the interferon response: the role of IRF-3 transcription factor.J Interferon Cytokine Res. 1999 Jan;19(1):1-13. doi: 10.1089/107999099314360. J Interferon Cytokine Res. 1999. PMID: 10048763 Review.
Cited by
-
The Structural Basis of IRF-3 Activation upon Phosphorylation.J Immunol. 2020 Oct 1;205(7):1886-1896. doi: 10.4049/jimmunol.2000026. Epub 2020 Aug 21. J Immunol. 2020. PMID: 32826280 Free PMC article.
-
IRF7: activation, regulation, modification and function.Genes Immun. 2011 Sep;12(6):399-414. doi: 10.1038/gene.2011.21. Epub 2011 Apr 14. Genes Immun. 2011. PMID: 21490621 Free PMC article. Review.
-
Human genome-wide RNAi screen identifies an essential role for inositol pyrophosphates in Type-I interferon response.PLoS Pathog. 2014 Feb 27;10(2):e1003981. doi: 10.1371/journal.ppat.1003981. eCollection 2014 Feb. PLoS Pathog. 2014. PMID: 24586175 Free PMC article.
-
ArfGAP Domain-Containing Protein 2 (ADAP2) Integrates Upstream and Downstream Modules of RIG-I Signaling and Facilitates Type I Interferon Production.Mol Cell Biol. 2017 Mar 1;37(6):e00537-16. doi: 10.1128/MCB.00537-16. Print 2017 Mar 15. Mol Cell Biol. 2017. PMID: 27956705 Free PMC article.
-
Differential Delivery of Genomic Double-Stranded RNA Causes Reovirus Strain-Specific Differences in Interferon Regulatory Factor 3 Activation.J Virol. 2018 Apr 13;92(9):e01947-17. doi: 10.1128/JVI.01947-17. Print 2018 May 1. J Virol. 2018. PMID: 29437975 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous
