Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1
Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1
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DOI：
10.1038/sj.gene.6364035
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发表时间：
2004-01-01
影响因子：
5
通讯作者：
Celada, A
中科院分区：
文献类型：
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作者：
Brucet, M;Marqués, L;Celada, A
与抗原加工相关的转运蛋白（Tap）-1和低分子量肽（Lmp）-2的基因对I类主要组织相容性复合体功能至关重要，并且共享共同的双向启动子。在小鼠骨髓源性巨噬细胞中，干扰素γ（IFN-γ）诱导Tap-1和上调Lmp-2，后者以低水平组成型表达。IFN-γ诱导独立于早期基因合成。IFN-γ诱导的mRNA非常稳定。在STAT 1基因敲除小鼠的巨噬细胞中，IFN-γ不诱导Tap-1或Lmp-2的表达。启动子中的几个区域可以由IFN-γ控制，例如Tap-1基因方向的近端和远端GAS盒、NF γ B和IRF-1盒。通过删除启动子，我们发现只有近端GAS和IRF-1盒是IFN-γ诱导Tap-1和Lmp-2所必需的。使用来自用IFN-γ处理30分钟的巨噬细胞的核提取物的实验和凝胶位移分析表明，STAT 1与GAS盒结合。用IFN-γ处理至少2小时的巨噬细胞的核提取物与IRF-1盒结合。这些结果表明STAT 1和IRF-1都是IFN-γ诱导Tap-1和Lmp-2基因所必需的。
The genes of the transporter associated with antigen processing (Tap)-1, and the low molecular weight peptide (Lmp)-2, are crucial for class I major histocompatibility complex function and share a common bidirectional promoter. In murine bone marrow-derived macrophages, interferon gamma (IFN-gamma) induced Tap-1 and upregulated Lmp-2, which is constitutively expressed at low levels. The IFN-gamma-induction was independent of early gene synthesis. The mRNA induced by IFN-gamma was very stable. In macrophages from STAT1 knockout mice, IFN-gamma did not induce the expression of Tap-1 or Lmp-2. Several areas in the promoter can be controlled by IFN-gamma, such as proximal and distal GAS boxes in the direction of the Tap-1 gene, NFgammaB and IRF-1 boxes. By making deletions of the promoter, we found that only the proximal GAS and IRF-1 boxes are required for IFN-gamma induction of Tap-1 and Lmp-2. Experiments using nuclear extracts from macrophages treated for 30 min with IFN-gamma and gel shift analysis indicated that STAT1 binds to the GAS box. The nuclear extracts from macrophages treated for at least 2 h with IFN-gamma bound to the IRF-1 box. These results indicate that both STAT1 and IRF-1 are required for the IFN-gamma induction of Tap-1 and Lmp-2 genes.