A Giant GTPase, Very Large Inducible GTPase-1, Is Inducible by IFNs 1

A Giant GTPase, Very Large Inducible GTPase-1, Is Inducible by IFNs 1
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巨大的 GTPase,非常大的诱导型 GTPase-1,可由 IFN 诱导 1

DOI:
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发表时间:
2003
影响因子:
4.4
通讯作者:
J. Howard
J. Howard
中科院分区:
医学2区
文献类型:
--
作者:
T. Klamp;U. Boehm;D. Schenk;K. Pfeffer;J. Howard

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对I型IFN(IFN-α和IFN-β)和II型IFN(IFN-γ)的复杂的、部分重叠的细胞应答涉及数百个基因,这些基因可以根据在先天性和适应性免疫中起作用的特定细胞程序来分类。在这些程序中,以前没有考虑过细胞自主抵抗各种病原体的机制,这些病原体是由专门的,主要是新的GTP酶家族介导的。我们在这里报告的鉴定和表征的一个新的GTdR家族,有助于细胞反应的I型和II型干扰素。我们将这个家族命名为非常大的诱导型GTP酶(VLIGs)。原型VLIG,VLIG-1,是一种强IFN-诱导的可溶性细胞质和核蛋白,分子量为280 kDa。VLIG-1的开放阅读框编码在一个非常大的外显子上,并且在典型的GTP结合基序之外,序列和结构预测表明与其他已知蛋白质家族没有显著关系的独特家族。在GTP酶超家族中,VLIG家族与介导细胞自主抗性的IFN诱导型GTP酶的关系比与其他GTP酶家族的关系更密切。此外,我们提供的证据表明,VLIG-1是多态性的小鼠不同的遗传背景,是一个小的基因家族的成员,在小鼠7号染色体上的一个保守的同源物位于人类11号染色体上。
The complex, partially overlapping, cellular responses to IFN type I (IFN-α and -β) and IFN type II (IFN-γ) involve several hundred genes that can be largely classified in terms of specific cellular programs functional in innate and adaptive immunity. Among these programs are previously unconsidered mechanisms of cell-autonomous resistance against various pathogens mediated by dedicated, largely novel families of GTPases. We report here the identification and characterization of a new GTPase family that contributes to the cellular response to both type I and type II IFNs. We name this family the very large inducible GTPases (VLIGs). The prototype VLIG, VLIG-1, is a strongly IFN-inducible, soluble, cytosolic and nuclear protein of 280 kDa. The open reading frame of VLIG-1 is encoded on a single very large exon, and outside the canonical GTP-binding motifs, sequence and structural prediction suggest a unique family without significant relationship to other known protein families. Within the GTPase superfamily the VLIG family is more closely related to IFN-inducible GTPases mediating cell-autonomous resistance than to other GTPase families. In addition, we provide evidence that VLIG-1 is polymorphic in mice of different genetic backgrounds and is a member of a small gene family on mouse chromosome 7 with a conserved homologue located on human chromosome 11.
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