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Ser386 phosphorylation of transcription factor IRF‐3 induces dimerization and association with CBP/p300 without overall conformational change
Author(s) -
Takahasi Kiyohiro,
Horiuchi Masataka,
Fujii Kiyonaga,
Nakamura Shingo,
Noda Nobuo N,
Yoneyama Mitsutoshi,
Fujita Takashi,
Inagaki Fuyuhiko
Publication year - 2010
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01427.x
Subject(s) - phosphorylation , transcription factor , biology , kinase , microbiology and biotechnology , irf1 , transcription (linguistics) , biochemistry , gene , linguistics , philosophy
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.