ZBP-99 defines a conserved family of transcription factors and regulates ornithine decarboxylase gene expression
ZBP-99 defines a conserved family of transcription factors and regulates ornithine decarboxylase gene expression
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DOI：
10.1006/bbrc.1999.1180
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发表时间：
1999-08-19
影响因子：
3.1
通讯作者：
Merchant, JL
中科院分区：
文献类型：
--
作者：
Law, DJ;Du, M;Merchant, JL
在调节鸟氨酸脱羧酶（ODC）基因表达的转录因子中，有那些与富含CC的启动子相互作用的转录因子，包括Spl和ZBP-89。Spl作为ODC和胃泌素启动子的反式激活因子发挥作用，ZBP-89作为ODC和胃泌素启动子的反式阻遏因子发挥作用。本研究报告的ZBP家族的第二个成员，也结合GC盒的克隆和表征。ZBP-99含有四个Kruppel型锌指，它们与ZBP-89中发现的锌指共有91%的氨基酸序列相似性和79%的序列同一性。此外，在两个基因的羧基末端区段中存在高度保守的氨基酸序列。尽管它们的结构相似，但这两种蛋白质在不同的位点编码，ZBP-89在染色体3q 21上，ZBP-99在1q32.1上。ZBP-99 cDNA的开放阅读框架编码一个99 kDa的蛋白质。电泳迁移率变动分析表明，ZBP-99蛋白特异性结合到富含CC的启动子元件的胃泌素和ODC基因。北方印迹分析表明，一个主要的ZBP-99转录本的5.6 kb的表达普遍在低水平，在胎盘和成人肾脏，肝脏和淋巴细胞的表达水平升高。用ZBP-99表达构建体和ODC报告构建体共转染AGS胃腺癌细胞和MT-29结肠腺癌细胞显示，ZBP-99分别抑制了两种细胞系中80%和60%的基础表达。总的来说，这些数据表明ZBP-99结合富含CC的启动子，并可能补充ZBP-89介导的活性。(C)北京：科学出版社.
Among transcription factors that regulate ornithine decarboxylase (ODC) gene expression are those that interact with CC-rich promoters, including Spl and ZBP-89. Spl functions as a transactivator and ZBP-89 as a transrepressor of both the ODC and gastrin promoters. This study reports the cloning and characterization of a second member of the ZBP family that also binds GC boxes. ZBP-99 contains four Kruppel-type zinc fingers that collectively share 91% amino acid sequence similarity and 79% sequence identity with those found in ZBP-89. In addition, there are highly conserved amino acid sequences in the carboxyterminal segments of the two genes. In spite of their structural similarities, the two proteins are encoded at distinct loci, ZBP-89 on chromosome 3q21 and ZBP-99 on 1q32.1. The predicted open reading frame of ZBP-99 cDNA encodes a 99-kDa protein. Electrophoretic mobility shift assays showed that ZBP-99 protein specifically binds to the CC-rich promoter elements of gastrin and ODC genes. Northern blot analysis showed that a major ZBP-99 transcript of 5.6 kb is expressed ubiquitously at low levels, with elevated expression levels in placenta and in adult kidney, liver, and lymphocytes. Cotransfection of AGS gastric adenocarcinoma and MT-29 colon adenocarcinoma cells with a ZBP-99 expression construct and with an ODC reporter construct show that ZBP-99 repressed basal expression in the two cell lines by 80 and 60%, respectively. Collectively, the data suggest that ZBP-99 binds CC-rich promoters and may complement the activities mediated by ZBP-89. (C) 1999 Academic Press.