Essential and non-redundant roses of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies

被引:198
作者
Kimura, T
Kadokawa, Y
Harada, H
Matsumoto, M
Sato, M
Kashiwazaki, Y
Tarutani, M
Tan, RSP
Takasugi, T
Matsuyama, T
Mak, TW
Noguchi, S
Taniguchi, T
机构
[1] UNIV TOKYO,FAC MED,DEPT IMMUNOL,BUNKYO KU,TOKYO 113,JAPAN
[2] OSAKA UNIV,INST MOL & CELLULAR BIOL,SUITA,OSAKA 565,JAPAN
[3] MEIJI MILK PROD CO LTD,MEIJI INST HLTH SCI,ODAWARA,KANAGAWA 250,JAPAN
[4] KANAGAWA ACAD SCI & TECHNOL,BIO SIGNAL PATHWAY PROJECT,ODAWARA,KANAGAWA 250,JAPAN
[5] AMGEN INST,TORONTO,ON M4X 1K9,CANADA
关键词
D O I
10.1046/j.1365-2443.1996.08008.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN-alpha and -beta) and type II (IFN-gamma) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2. The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1). Results: We generated mice lacking p48 by gene targeting. We show that p48 plays an essential role in both type I and type II IFN responses; activation of LFN-inducible genes and establishment of the antiviral state by IFN-alpha or -gamma are both severely impaired, and ISRE-binding activities induced by both IFNs are absent in the p48-negative embryonic fibroblasts (EFs). Furthermore, we generated mice deficient for both p48 and IRF-1 and found that at least one IFN-inducible gene is dependent on both factors. Conclusions: p48 and LRF-1 do not perform redundant functions in the cell, but rather complement one another in both type I and II IFN responses.
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页码:115 / 124
页数:10
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