WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappaB activation.

Viral infection causes activation of the transcription factors NF-kappaB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. The mitochondrial outer membrane protein VISA acts as a critical adapter for assembling a virus-induced complex that signals NF-kappaB and IRF3 activation. Using a biochemical purification approach, ...
we identified the WD repeat protein WDR5 as a VISA-associated protein. WDR5 was recruited to VISA in a viral infection dependent manner. Viral infection also caused translocation of WDR5 from the nucleus to mitochondria. Knockdown of WDR5 impaired the formation of virus-induced VISA-associated complex. Consistently, knockdown of WDR5 inhibited virus-triggered activation of IRF3 and NF-kappaB as well as transcription of the IFNB1 gene. These findings suggest that WDR5 is essential in assembling a virus-induced VISA-associated complex and plays an important role in virus-triggered induction of type I IFNs.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, DNA Primers, Histone-Lysine N-Methyltransferase, Humans, Immunity, Innate, Interferon Regulatory Factor-3, Mice, Molecular Biology, NF-kappa B, Plasmids, Proteins, RNA, Viral, Reverse Transcriptase Polymerase Chain Reaction, Toll-Like Receptors, Transcriptional Activation, Virus Diseases, Viruses
Proc. Natl. Acad. Sci. U.S.A.
Date: Jan. 12, 2010
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