Meta-Biol

• Pathways

Human IRF3 is activated through a two step phosphorylation in the C-terminal domain mediated by TBK1 and/or IKKi. It requires Ser386 and/or Ser385 (site 1) and a cluster of serine/threonine residues between Ser396 and Ser405 (site 2) (Panne et al. 2007). Phosphorylated residues at site 2 alleviate autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitate phosphorylation at site 1. Phosphorylation at site 1 is required for IRF3 dimerization.

IRF3 and IRF7 transcription factors possess distinct structural characteristics; IRF7 is phosphorylated on Ser477 and Ser479 residues (Lin R et al. 2000). TRAF6 mediated ubiquitination of IRF7 is also required and essential for IRF7 phosphorylation and activation. The K-63 linked ubiquitination occurs on the last three C-terminal lysine sites (positions 444, 446, and 452) of human IRF7 independently of its C-terminal functional phosphorylation sites.(Ning et al. 2008).