A novel mechanism of nuclear factor-κB regulation by adenoviral protein 14.7K
A novel mechanism of nuclear factor-κB regulation by adenoviral protein 14.7K
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DOI：
10.1111/j.1365-2567.2005.02277.x
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发表时间：
2006-02-01
期刊：
影响因子：
6.4
通讯作者：
Chen, YH
中科院分区：
文献类型：
--
作者：
Carmody, RJ;Maguschak, K;Chen, YH
病毒已经进化出许多不同的方法来逃避免疫攻击。腺病毒E3蛋白14.7K有效抑制抗病毒免疫和炎症。然而，这种影响的潜在机制尚不清楚。本研究表明，14.7K是toll样受体（TLR）或肿瘤坏死因子（TNF）受体信号传导后核因子(NF)- κ B转录活性的有效抑制剂。NF-kappa B活性的抑制发生在I -kappa B α降解和NF-kappa B转运到细胞核的下游。NF-kappa B DNA结合分析表明，14.7K特异性抑制p50同型二聚体的DNA结合，这种抑制是通过14.7K与p50的相互作用介导的。我们提出14.7K通过直接阻断p50与DNA的结合来抑制NF-kappa B的活性，这是其抗炎特性的基础。我们的数据还表明p50同源二聚体依赖性转录在炎症中的作用。
Viruses have evolved many different ways to evade immune attacks. The adenoviral E3 protein 14.7K effectively inhibits antiviral immunity and inflammation. However, the underlying mechanism for this effect is unclear. Here we show that 14.7K is a potent inhibitor of nuclear factor (NF)-kappa B transcriptional activity following Toll-like receptor (TLR) or tumour necrosis factor (TNF) receptor signalling. The inhibition of the NF-kappa B activity occurs downstream of I kappa B alpha degradation and NF-kappa B translocation into the nucleus. Analysis of NF-kappa B DNA binding reveals that 14.7K specifically inhibits p50 homodimer DNA binding and that this inhibition is mediated through the interaction of 14.7K with p50. We propose that 14.7K inhibits NF-kappa B activity through directly blocking p50 binding to DNA and that this is the basis for its anti-inflammatory properties. Our data also indicate a role for p50 homodimer-dependent transcription in inflammation.