Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-β-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth
Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-β-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth
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DOI：
10.1074/jbc.273.40.25929
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发表时间：
1998-10-02
影响因子：
4.8
通讯作者：
Urrutia, R
中科院分区：
文献类型：
--
作者：
Cook, T;Gebelein, B;Urrutia, R
Sp1样锌指转录因子参与细胞生长和分化的调控。最近的证据表明，哺乳动物细胞表达新的，但未表征的，Sp1样蛋白刺激了寻找这个家庭的新成员。我们和其他人最近报道，转化生长因子（TGF）-β调节基因TIEG编码一种新的Sp1样蛋白，抑制培养细胞中的细胞生长。在这里，我们报告的鉴定，核定位，DNA结合活性，转录抑制活性，和生长抑制作用的TIEG 2，一种新的TGF-β诱导基因TIEG相关。TIEG 2在人体组织中广泛表达，在胰腺和肌肉中富集。TIEG 2与TIEG 1在锌指区域内具有91%的同源性，在N末端内具有44%的同源性。TIEG 2是一种核蛋白，其一级结构预测，在体外与Sp1样DNA序列特异性结合，并可抑制转染的中国仓鼠卵巢上皮细胞中含有Sp1样结合位点的启动子。此外，使用[H-3]胸苷摄取和MTS（3-（4，3-二甲基噻唑-2基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑）测定的功能研究证明，中国仓鼠卵巢细胞中TIEG 2的过表达抑制细胞增殖。因此，TIEG 2与TIEG 1一起定义了参与细胞生长调节的TGF-β诱导型Sp1样蛋白的新亚家族。
Sp1-like zinc finger transcription factors are involved in the regulation of cell growth and differentiation. Recent evidence demonstrating that mammalian cells express novel, yet uncharacterized, Sp1-like proteins has stimulated a search for new members of this family. We and others have recently reported that the transforming growth factor (TGF)-beta-regulated gene TIEG encodes a new Sp1-like protein that inhibits cell growth in cultured cells. Here we report the identification, nuclear localization, DNA binding activity, transcriptional repression activity, and growth inhibitory effects of TIEG2, a novel TGF-beta-inducible gene related to TIEG. TIEG2 is ubiquitously expressed in human tissues, with an enrichment in pancreas and muscle. TIEG2 shares 91% homology with TIEG1 within the zinc finger region and 44% homology within the N terminus. Biochemical characterization reveals that TIEG2 is a nuclear protein, which, as predicted from the primary structure, specifically binds to an Sp1-like DNA sequence in vitro and can repress a promoter containing Sp1-Like binding sites in transfected Chinese hamster ovary epithelial cells. Furthermore, functional studies using [H-3]thymidine uptake and MTS (3-(4,3-dimethyltiazol-2 yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl) -2H-tetrazolium) assays demonstrate that the overexpression of TIEG2 in Chinese hamster ovary cells inhibits cell proliferation. Thus, TIEG2, together with TIEG1, defines a new subfamily of TGF-beta-inducible Sp1-Like proteins involved in the regulation of cell growth.