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T细胞转录因子NFATc和NFATp的人类及小鼠基因的克隆与染色体定位

Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp.

作者信息

Li X, Ho S N, Luna J, Giacalone J, Thomas D J, Timmerman L A, Crabtree G R, Francke U

机构信息

Howard Hughes Medical Institute, Stanford University Medical Center, CA 94305-5428.

出版信息

Cytogenet Cell Genet. 1995;68(3-4):185-91. doi: 10.1159/000133910.

DOI:10.1159/000133910
PMID:7842733
Abstract

The nuclear factor of activated T cells (NFAT) is a transcription factor complex involved in the activation of cytokines and cell surface molecules associated with coordinating the actions of different cells required for an immune response. Two different genes have recently been cloned that encode proteins capable of functioning as the pre-existing (p) and cytosolic (c) component of the NFAT transcription complex, NFATc of human and NFATp of murine origin (Northrop et al., 1994; McCaffrey et al., 1993b). We report here the partial cDNA cloning of the murine homolog of NFATc and the human homolog of NFATp, and the chromosomal localization of both genes in both species to conserved syntenic regions. Through the use of mapping panels of human x Chinese hamster and mouse x rodent cells hybrids, the NFATc genes were mapped to human and mouse chromosomes 18. By analyzing a chromosome 18 radiation hybrid panel, the human NFATc gene was localized to the q terminus, closely linked to STS marker D18S497. The murine Nfatc gene was sublocalized to chromosome band 18E4 by FISH. The NFATp genes were mapped by somatic cell hybrid analysis to human chromosome 20 and mouse chromosome 2. Human NFATp was assigned to chromosome region 20q13.2-->q13.3 by FISH. Based on the conserved syntenic region on human chromosome 20 and mouse chromosome 2, murine Nfatp is predicted to reside in the vicinity of a mutant locus wasted. Homozygous wst/wst mice display a phenotype reminiscent of severe combined immune deficiency or ataxia telangiectasia, disorders that could therefore be considered candidates for NFATp mutations.

摘要

活化T细胞核因子(NFAT)是一种转录因子复合物,参与细胞因子和细胞表面分子的激活,这些分子与协调免疫反应所需的不同细胞的作用相关。最近克隆了两个不同的基因,它们编码的蛋白质能够作为NFAT转录复合物的预先存在的(p)和胞质(c)成分发挥作用,即人类的NFATc和鼠源的NFATp(诺斯罗普等人,1994年;麦卡弗里等人,1993年b)。我们在此报告鼠源NFATc同源物和人类NFATp同源物的部分cDNA克隆,以及这两个基因在两个物种中于保守同线区域的染色体定位。通过使用人×中国仓鼠和小鼠×啮齿动物细胞杂交的定位板,NFATc基因被定位到人类和小鼠的18号染色体上。通过分析18号染色体辐射杂种板,人类NFATc基因被定位到q末端,与STS标记D18S'497紧密连锁。通过荧光原位杂交(FISH)将鼠源Nfatc基因亚定位到18E4染色体带。通过体细胞杂交分析将NFATp基因定位到人类20号染色体和小鼠2号染色体上。通过FISH将人类NFATp定位到染色体区域20q13.2→q13.3。基于人类20号染色体和小鼠2号染色体上的保守同线区域,预计鼠源Nfatp位于突变位点wasted附近。纯合的wst/wst小鼠表现出一种类似于严重联合免疫缺陷或共济失调毛细血管扩张症的表型,因此这些疾病可被视为NFATp突变的候选疾病。

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Alternative splicing and expression of human and mouse NFAT genes.人类和小鼠NFAT基因的可变剪接与表达
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Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells.Ets与NF-κB/NFAT蛋白之间的物理相互作用在它们对T细胞中人免疫缺陷病毒增强子的协同激活中发挥重要作用。
J Virol. 1997 May;71(5):3563-73. doi: 10.1128/JVI.71.5.3563-3573.1997.
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Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import.钙调神经磷酸酶与控制核输入的转录因子NFAT1的一个结构域之间的相互作用。
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