Phospho-IRF-3 (Ser396) Antibody #4961

Interferon regulatory factors (IRFs) comprise a family of transcription factors that function within the Jak/Stat pathway to regulate interferon (IFN) and IFN-inducible gene expression in response to viral infection (1). IRFs play an important role in pathogen defense, autoimmunity, lymphocyte development, cell growth, and susceptibility to transformation. The IRF family includes nine members: IRF-1, IRF-2, IRF-9/ISGF3γ, IRF-3, IRF-4 (Pip/LSIRF/ICSAT), IRF-5, IRF-6, IRF-7, and IRF-8/ICSBP. All IRF proteins share homology in their amino-terminal DNA-binding domains. IRF family members regulate transcription through interactions with proteins that share similar DNA-binding motifs, such as IFN-stimulated response elements (ISRE), IFN consensus sequences (ICS), and IFN regulatory elements (IRF-E) (2).

IRF3 can inhibit cell growth and plays a critical role in controling the expression of genes in the innate immune response (1-4). In unstimulated cells, IRF3 is present in the cytoplasm. Viral infection results in phosphorylation of IRF3, leading to its translocation to the nucleus, where it activates promoters containing IRF3-binding sites. Phosphorylation of IRF3 occurs at a cluster of serine and threonine residues in the carboxy-terminus between residues 385 and 405 leading to its association with the coactivator protein, p300/CBP which promotes DNA binding and transcriptional activity (5). During infection, IRF3 is likely activated through a pathway that includes activation of Toll-like receptors and of a kinase complex that includes IKKe and TBK1 (6,7). IRF-3 is phosphorylated at Ser396 following viral infection, expression of viral nucleocapsid, and double stranded RNA treatment, and these events play a role in its activation (8).