The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3

Hwijin Kim & Brian Seed. Nature immunology 11, 743 – 750 (2010)

Speaker: Wei-Min Hung (洪偉珉)                                 Time: 13:10 ~ 14:00, May. 4, 2011

Commentator: Dr. Hsiao-Sheng Liu (劉校生 老師)     Place: Room 601

Abstract:

The innate antiviral response requires the induction of genes and proteins that limit viral replication¹. Among these, the interferon β (IFN-β) gene is regulated through the cooperation of AP-1, NF-κB, interferon regulatory factor 3 (IRF3) and the coactivators p300/CREB-binding protein (CBP)². Although cellular induction of cytokines is essential for suppression of viral propagation, mammalian cells have also developed many mechanisms to prevent spontaneous induction and production of type I interferon. In this study, the authors identified a regulator, MafB, which regulated the interferon response. The results showed that MafB acted as a weak positive regulator of transcription at the IFNB1 promoter through activity at transcription factor AP-1 site. After adventitious binding of activated IRF3 to the promoter, MafB interfered with IRF3 activity by impairing recruitment of the transcriptional coactivator CBP to IRF3. But after viral infection, the recruitment of IRF3 to the IFNB1 promoter increased substantially that counteract this buffering role of MafB to facilitate the IFNB1 activation. Therefore, MafB could create an inhibitory threshold that buffered cells against unwarranted induction of type I interferon. In insulin-dependent diabetes mellitus (IDDM), the decrease of insulin production might be due to the destruction of pancreatic β cells by viral infection³. Because MafB expression was higher in human β cells, the authors suggested that β cells with high expression of MafB could be vulnerable to viral infections associated with the IDDM. Collectively, MafB expression and regulation have important consequences for type I interferon responses.

References:

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2.     Hiscott, J. Triggering the innate antiviral response through IRF-3 activation. J. Biol. Chem. 282, 15325-15329 (2007).

3.     Fairweather D, Rose NR. Type 1 diabetes: virus infection or autoimmune disease? Nat. Immunol. 3, 338 - 340 (2002)