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干扰素调节因子7:在适应性免疫相关基因调控中的新作用

IRF-7: new role in the regulation of genes involved in adaptive immunity.

作者信息

Sgarbanti Marco, Marsili Giulia, Remoli Anna Lisa, Orsatti Roberto, Battistini Angela

机构信息

Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.

出版信息

Ann N Y Acad Sci. 2007 Jan;1095:325-33. doi: 10.1196/annals.1397.036.

Abstract

The interferon regulatory factor 7 (IRF-7), a member of the IRF family of transcription factors, is a key player in the innate immune response against viral infections. Constitutive expression of IRF-7 is limited to peripheral blood lymphocytes and dendritic cells while in most cell types its expression can be induced by type I interferon (INF). IRF-7 is sequestered in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, it becomes phosphorylated by TBK and IKK-i kinases. Phosphorylated IRF-7 migrates in the nucleus where it can activate IFN type I genes and other interferon-stimulated genes (ISGs). Here we report that the overexpression of a constitutively active form of IRF-7 binds and positively regulates the transcriptional activity of the promotor of IRF-1 and low molecular mass polypeptide-2 (LMP-2), two proteins that play a key role in adaptive immunity. The so far unrecognized role of IRF-7 in LMP-2 stimulation points to IRF-7 as a transcriptional regulator that bridges innate and adaptive immunity.

摘要

干扰素调节因子7(IRF-7)是转录因子IRF家族的成员,是针对病毒感染的先天免疫反应中的关键因子。IRF-7的组成型表达仅限于外周血淋巴细胞和树突状细胞,而在大多数细胞类型中,其表达可由I型干扰素(INF)诱导。IRF-7在未感染细胞的细胞质中被隔离,在病毒感染、双链RNA(dsRNA)或Toll样受体(TLR)信号传导后,它被TBK和IKK-i激酶磷酸化。磷酸化的IRF-7迁移到细胞核中,在那里它可以激活I型干扰素基因和其他干扰素刺激基因(ISG)。在这里,我们报告说,组成型活性形式的IRF-7的过表达结合并正向调节IRF-1和低分子量多肽-2(LMP-2)启动子的转录活性,这两种蛋白质在适应性免疫中起关键作用。IRF-7在LMP-2刺激中迄今未被认识的作用表明,IRF-7是一种连接先天免疫和适应性免疫的转录调节因子。

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