A family of interferon (IFN) regulatory factors (IRFs) have been shown to play a role in transcription of IFN genes as well as IFN-stimulated genes. The IRF-3 gene encodes a 50-kDa protein that binds specifically to the IFN-stimulated response element (ISRE) (1). 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. Phosphorylation at Serine 396 through Serine 405 alleviates autoinhibition to allow interaction with CREB-binding protein and facilitates phosphorylation at Serine 385 or Serine 386 (2). Serine 386 is suggested to be the target of the IRF-3 kinase and critical determinant for the activation of IRF-3 (3).
Toll-like receptor signaling pathway
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