Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch - PubMed (original) (raw)

. 2007 Aug 3;282(31):22816-22.

doi: 10.1074/jbc.M703019200. Epub 2007 May 25.

Affiliations

• PMID: 17526488
• DOI: 10.1074/jbc.M703019200

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Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch

Daniel Panne et al. J Biol Chem. 2007.

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Abstract

The transcription factor interferon regulatory factor 3 (IRF-3) regulates genes in the innate immune response. IRF-3 is activated through phosphorylation by the kinases IKK epsilon and/or TBK1. Phosphorylation results in IRF-3 dimerization and removal of an autoinhibitory structure to allow interaction with the coactivators CBP/p300. The precise role of the different phosphorylation sites has remained controversial. Using purified proteins we show that TBK1 can directly phosphorylate full-length IRF-3 in vitro. Phosphorylation at residues in site 2 (Ser(396)-Ser(405)) alleviates autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitates phosphorylation at site 1 (Ser(385) or Ser(386)). Phosphorylation at site 1 is, in turn, required for IRF-3 dimerization. The data support a two-step phosphorylation model for IRF-3 activation mediated by TBK1.

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