The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3.
The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3.
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病毒感染诱导I型干扰素（IFN-α和-β），其在自我扩增反应中招募未暴露的细胞。我们报告说，转录因子MAFB阻挠自动扩增的亚稳态开关行为。MAFB通过在AP-1样位点的活性在IFN-β启动子处充当弱阳性基础转录调节剂。干扰素诱导子将转录因子IRF 3募集到启动子，于是MAFB充当转录拮抗剂，削弱CREB结合蛋白（CBP）与IRF 3的相互作用。数学建模支持这样的观点，即MAFB在启动子上的预先定位允许系统对IRF 3活性的波动迅速作出响应。人胰岛β细胞中MAFB的高表达可能增加细胞对与I型糖尿病病因学相关的病毒感染的脆弱性。
Viral infections induce Type I interferons (IFN-α and -β) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MAFB thwarts auto-amplification by a metastable switch behavior. MAFB acts as a weak positive basal regulator of transcription at the IFN-β promoter through activity at AP-1-like sites. Interferon elicitors recruit the transcription factor IRF3 to the promoter, whereupon MAFB acts as a transcriptional antagonist, impairing the interaction of CREB-binding protein (CBP) with IRF3. Mathematical modeling supports the view that prepositioning of MAFB on the promoter allows the system to respond rapidly to fluctuations in IRF3 activity. Elevated expression of MAFB in human pancreatic islet β-cells might increase cellular vulnerability to viral infections associated with the etiology of type I diabetes.