Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change.
Genes Cells
; 15(8): 901-10, 2010 Aug.
Article
en En
| MEDLINE
| ID: mdl-20604809
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serina
/
Factores de Transcripción p300-CBP
/
Factor 3 Regulador del Interferón
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Genes Cells
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón