CDNA STRUCTURES AND REGULATION OF 2 INTERFERON-INDUCED HUMAN MX PROTEINS

CDNA STRUCTURES AND REGULATION OF 2 INTERFERON-INDUCED HUMAN MX PROTEINS
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DOI:
10.1128/mcb.9.11.5062
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发表时间:
1989-11-01
影响因子:
5.3
通讯作者:
STAEHELI, P
STAEHELI, P
中科院分区:
生物学2区
文献类型:
--
作者:
AEBI, M;FAH, J;STAEHELI, P

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用干扰素处理的人细胞合成两种与小鼠Mx1蛋白高度同源的蛋白,该蛋白先前已被确定为干扰素诱导小鼠细胞抵抗流感病毒的介质。使用小鼠Mx1 cDNA作为杂交探针,我们分离了两个不同的人类Mx基因的cDNA克隆,命名为MxA和MxB。在人成纤维细胞中,α干扰素(IFN-. α)、IFN-. β强烈诱导MxA和MxB的表达。新城疫病毒,以及较小程度的IFN- γ…MxA蛋白和MxB蛋白的分子质量分别为76千道尔顿和73千道尔顿,它们的序列有63%相同。比较人和小鼠的Mx蛋白发现,人的MxA和小鼠的Mx2是最密切相关的蛋白,具有77%的序列同源性。在其氨基末端附近,人和小鼠Mx蛋白含有53个相同的氨基酸块和非常高序列相似性的额外区域。这些保守序列也存在于双链rna诱导的鱼类基因中,这表明它们可能构成了Mx蛋白的一个重要功能域。小鼠Mx蛋白在ifn处理的小鼠细胞的细胞核中积累,与之相反,两种人Mx蛋白都在ifn处理的细胞的细胞质中积累。
Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator of interferon-induced cellular resistance of mouse cells against influenza viruses. Using murine Mx1 cDNA as a hybridization probe, we have isolated cDNA clones originating from two distinct human Mx genes, designated MxA and MxB. In human fibroblasts, expression of MxA and MxB is strongly induced by alpha interferon (IFN-.alpha.), IFN-.beta., Newcastle disease virus, and, to a much lesser extent, IFN-.gamma.. MxA and MxB proteins have molecular masses of 76 and 73 kilodaltons, respectively, and their sequences are 63% identical. A comparison of human and mouse Mx proteins revealed that human MxA and mouse Mx2 are the most closely related proteins, showing 77% sequence identity. Near their amino termini, human and mouse Mx proteins contain a block of 53 identical amino acids and additional regions of very high sequence similarity. These conserved sequences are also present in a double-stranded RNA-inducible fish gene, which suggests that they may constitute a functionally important domain of Mx proteins. In contrast to mouse Mx1 protein, which accumulates in the nuclei of IFN-treated mouse cells, the two human Mx proteins both accumulate in the cytoplasm of IFN-treated cells.