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Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change.
- Source :
-
Genes to Cells . Aug2010, Vol. 15 Issue 8, p901-910. 10p. 2 Color Photographs, 2 Charts, 4 Graphs. - Publication Year :
- 2010
-
Abstract
- The transcription factor IRF-3 is activated by microbial invasions and produces a variety of cytokines including type-I interferon. Upon microbial infection, IRF-3 is phosphorylated at its C-terminal regulatory domain, then oligomerized, translocated into the nucleus, and here it binds to CBP/p300. Although a number of studies have been reported investigating the activation mechanism of IRF-3, there are a number of unresolved issues, especially on the phosphorylation sites, the oligomerization process and the binding mechanism with CBP/p300. In this report, the phosphorylated IRF-3 regulatory domain (IRF-3 RD) was prepared using the kinase IKK-i, and the active form of phosphorylated IRF-3 RD was identified. The paper also reports the crystal structure of the active form of the phosphorylated IRF-3 RD. Furthermore, the phosphorylation of Ser386 was found to be essential for its dimerization and binding with CBP/p300 using mutational analysis and mass spectrometry. Thus, we conclude that the phosphorylation of Ser386 is essential for activation of IRF-3. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13569597
- Volume :
- 15
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Genes to Cells
- Publication Type :
- Academic Journal
- Accession number :
- 52267378
- Full Text :
- https://doi.org/10.1111/j.1365-2443.2010.01427.x