Interferon regulatory factors comprise a family of transcription factors that function within the Jak/Stat pathway to regulate interferon and IFN-inducible gene expression in response to viral infection. 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, 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, IFN consensus sequences, and IFN regulatory elements.While IRF family members generally function in innate immune responses, IRF-6 has not been associated in that role. Original studies of IRF-6 found that mutation of the IRF-6 gene caused Van der Woude Syndrome, an autosomal dominant disorder resulting in mouth abnormalities including cleft lip and palate. IRF-6 knockouts show a hyperproliferative epidermis that fails to undergo keratinocyte differentiation. IRF-6 has also been found to interact with the mammary tumor suppressor maspin, and like maspin is expressed in normal mammary epithelial but reduced or absent in breast carcinoma. Cellular proliferation may promote IRF-6 phosphorylation leading to its proteasomal dependent degradation.
[1] Taniguchi, T. et al. (2001) Annu Rev Immunol 19, 623-55.
[2] Honda, K. and Taniguchi, T. (2006) Nat Rev Immunol 6, 644-58.
[3] Kondo, S. et al. (2002) Nat Genet 32, 285-9.
[4] Richardson, R.J. et al. (2006) Nat Genet 38, 1329-34.
[5] Bailey, C.M. et al. (2005) J Biol Chem 280, 34210-7.
[6] Bailey, C.M. et al. (2008) Mol Cell Biol 28, 2235-43.
