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首页> 外文期刊>The FEBS journal >Ciz1, a p21(Cip1/Waf1)-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog
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Ciz1, a p21(Cip1/Waf1)-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog

机译:Ciz1,一种与p21(Cip1 / Waf1)相互作用的锌指蛋白和DNA复制因子,是人类基本同源增强子的新型分子伴侣

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摘要

Enhancer of rudimentary homolog (Drosophila) (ERH) is a small, highly conserved, nuclear protein with a unique three-dimensional structure, whose gene has been identified in animals, plants and protists, but not in fungi. Involvement of ERH in fundamental processes such as regulation of pyrimidine metabolism, cell cycle progression, transcription and cell growth control has been suggested. Here, employing a yeast two-hybrid system, a glutathione S-transferase pull-down assay and tandem MS, we demonstrate that Ciz1 is a bona fide interactor of human ERH. Ciz1 is a nuclear zinc finger protein interacting with p21(Cip1/Waf1), a universal inhibitor of cyclin-dependent kinases, and is a DNA replication factor. The region of Ciz1 necessary for the interaction with ERH spans residues 531-644, encompassing its first zinc finger motif. This region overlaps the p21(Cip1/Waf1)-binding site, suggesting that the interaction with ERH could block the binding of p21(Cip1/Waf1) by Ciz1 in the cell. When ERH and Ciz1 are coexpressed in HeLa cells, Ciz1 recruits ERH to DNA replication foci.
机译:原始同源物(果蝇)增强子(ERH)是一种高度保守的小核蛋白,具有独特的三维结构,其基因已在动物,植物和原生生物中被鉴定出来,但在真菌中却未被鉴定。已建议ERH参与基本过程,例如嘧啶代谢的调节,细胞周期进程,转录和细胞生长控制。在这里,采用酵母双杂交系统,谷胱甘肽S-转移酶下拉测定和串联MS,我们证明Ciz1是人类ERH的真正的相互作用者。 Ciz1是与p21(Cip1 / Waf1)(一种细胞周期蛋白依赖性激酶的通用抑制剂)相互作用的核锌指蛋白,是DNA复制因子。与ERH相互作用所必需的Ciz1区域跨越残基531-644,包括其第一个锌指基序。该区域与p21(Cip1 / Waf1)结合位点重叠,这表明与ERH的相互作用可能会阻断细胞中Ciz1对p21(Cip1 / Waf1)的结合。当ERH和Ciz1在HeLa细胞中共表达时,Ciz1将ERH募集到DNA复制灶。

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