Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes
Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes
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DOI：
10.1074/jbc.273.44.29210
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发表时间：
1998-10-30
影响因子：
4.8
通讯作者：
Pitha, PM
中科院分区：
文献类型：
--
作者：
Au, WC;Moore, PA;Pitha, PM
干扰素调节因子家族在调节细胞对病毒感染和包括干扰素在内的细胞因子的反应中起着重要作用。参与IFNB基因转录激活的转录因子已被广泛研究。然而，病毒激活IFNA基因表达的分子机制仍有待确定。最近，我们发现了一个新的IRF-7亚型，命名为IRF-7H，它编码一个514个氨基酸的蛋白质，与IRF-3关系最密切。IRF-7的表达仅限于淋巴细胞类型，并可被病毒、脂多糖和IFNA诱导。IRF-7H的功能鉴定表明，其DNA结合区存在一个位于其羧基末端的反式激活结构域。IRF-7H的过表达导致瞬时转染实验中IFNA启动子的激活，并强烈增强病毒介导的该启动子的激活。而在未感染的细胞中，过表达的IRF-7H主要存在于细胞质中，病毒感染促进了IRF-7H向细胞核的转移；IRF-3的过表达干扰了病毒诱导的IRF-7H的转位。因此，IRF-7具有与IRF-3相似的功能；然而，IRF-7在淋巴样细胞(表达IFNA的细胞类型)中的优先表达表明IRF-7可能在调节IFNA基因的表达中发挥关键作用。
The family of interferon regulatory factors (IRFs) plays an important role in modulating cellular responses to viral infection and cytokines, including IFNs. The transcription factors that are involved in the transcriptional activation of the IFNB gene have been extensively studied. However, the molecular mechanism by which virus activates the expression of the IFNA gene remains to be defined. Recently, we have identified a new IRF-7 isoform, denoted as IRF-7H, which encodes a protein of 514 amino acids and is most closely related to the IRF-3. The expression of IRF-7 is restricted to the lymphoid cell types and is inducible by virus, lipopolysaccharide, and IFNA. The functional characterization of IRF-7H reveals a presence of transactivation domain located carboxyl-terminal to its DNA binding domain. Overexpression of IRF-7H results in an activation of IFNA promoter in transient transfection assay and a strong enhancement of virus-mediated activation of this promoter. Whereas in uninfected cells, overexpressed IRF-7H is present mainly in the cytoplasm, viral infection facilitates the transfer of IRF-7H to the nucleus; overexpression of IRF-3 interferes with the virus-induced translocation of IRF-7H. Thus, IRF-7 exhibits functional similarity to IRF-3; however, the preferential expression of IRF-7 in lymphoid cells (the cell type that expresses IFNA) suggests that IRF-7 may play a critical role in regulating the IFNA gene expression.