Lipopolysaccharide activates the expression of ISG15-specific protease UBP43 via interferon regulatory factor 3
Lipopolysaccharide activates the expression of ISG15-specific protease UBP43 via interferon regulatory factor 3
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DOI：
10.1074/jbc.m111527200
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发表时间：
2002-04-26
影响因子：
4.8
通讯作者：
Zhang, DE
中科院分区：
文献类型：
--
作者：
Malakhova, O;Malakhov, M;Zhang, DE
UBP43是一种蛋白酶，可以特异性地从靶标上去除泛素样蛋白ISG15。在巨噬细胞和单核细胞系中检测到最高水平的UBP43表达。巨噬细胞在宿主防御细菌和病毒感染中起重要作用。细菌细胞壁的脂多糖（LPS）可以模拟细菌并激活单核细胞/巨噬细胞引起炎症反应。在这里，我们报道LPS强烈激活巨噬细胞中UBP43的表达，这与UBP43蛋白水平的变化是平行的。UBP43启动子中的两个干扰素调节因子（IRF）结合位点负责LPS诱导UBP43的表达，以及UBP43启动子的基础活性。我们已经确定了IRF家族的两个成员（IRF-2和IRF-3）专门结合这些位点。IRF-3在lps诱导的UBP43基因激活中起主要作用，而IRF-2赋予UBP43启动子基本的转录活性。此外，我们证明LPS处理增加了巨噬细胞中isg15偶联物的数量。ISG15和UBP43的协同诱导表明，ISG15的结合是一个动态的过程，在先天免疫应答过程中，ISG15修饰应保持一个关键的平衡。
UBP43 is a protease that specifically removes a ubiquitin-like protein, ISG15, from its targets. Highest levels of UBP43 expression are detected in macrophages and in cell lines of monocytic lineage. Macrophages are important in host defense against bacterial and viral infections. The lipopolysaccharide (LPS) of the bacterial cell wall can mimic bacteria and activate monocytes/macrophages to provoke inflammatory responses. Here, we report that LPS strongly activates UBP43 expression in macrophages, which is paralleled by changes in UBP43 protein levels. Two interferon regulatory factor (IRF) binding sites in the UBP43 promoter are responsible for the induction of UBP43 expression by LPS, as well as for basal UBP43 promoter activity. We have identified two members of the IRF family (IRF-2 and IRF-3) that specifically bind to these sites. IRF-3 plays a primary role in the LPS-inducible activation of the UBP43 gene and IRF-2 confers a basal transcriptional activity to the UBP43 promoter. Furthermore, we demonstrate that LPS treatment increases the amount of ISG15-conjugates in macrophages. Coordinated induction of ISG15 and UBP43 suggests that ISG15 conjugation is a dynamic process and that a critical balance of ISG15-modification should be maintained during innate immune response.