Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes

被引:255
作者
Au, WC
Moore, PA
LaFleur, DW
Tombal, B
Pitha, PM
机构
[1] Johns Hopkins Univ, Sch Med, Oncol Ctr, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21231 USA
[3] Human Genome Sci Inc, Rockville, MD 20850 USA
关键词
D O I
10.1074/jbc.273.44.29210
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:29210 / 29217
页数:8
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