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  • 标题:WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-κB activation
  • 本地全文:下载
  • 作者:Yan-Yi Wang ; Li-Juan Liu ; Bo Zhong
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2010
  • 卷号:107
  • 期号:2
  • 页码:815-820
  • DOI:10.1073/pnas.0908967107
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Viral infection causes activation of the transcription factors NF-{kappa}B 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-{kappa}B 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-{kappa}B 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.
  • 关键词:innate immunity ; interferon ; mitochondrial signal transduction
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