Isolation of two cDNAs encoding zinc finger proteins which bind to the alpha 1-antitrypsin promoter and to the major histocompatibility complex class I enhancer

Isolation of two cDNAs encoding zinc finger proteins which bind to the alpha 1-antitrypsin promoter and to the major histocompatibility complex class I enhancer
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分离编码锌指蛋白的两个 cDNA,这些锌指蛋白与 α1-抗胰蛋白酶启动子和主要组织相容性复合物 I 类增强子结合

DOI:
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发表时间:
1991
期刊:
Nucleic Acids Res.
影响因子:
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通讯作者:
R. Cortese
R. Cortese
中科院分区:
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文献类型:
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作者:
C. Mitchelmore;C. Traboni;R. Cortese

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已分离出编码 DNA 结合蛋白(AT-BP1 和 AT-BP2)的两个部分 cDNA。当从 lambda gt11 溶原菌制备时,这两种蛋白均与 α1-抗胰蛋白酶启动子的 B 结构域结合,该启动子对于 α1-抗胰蛋白酶的肝脏特异性表达非常重要。对编码这些蛋白质的 cDNA 序列的分析表明,两者都含有两个 Cys2-His2 类型的锌指,后面跟着一段 20 个氨基酸的高酸性序列。 AT-BP1 包含第二个假定的 DNA 结合结构域,由 SPKK(Ser-Pro-Lys/Arg-Lys/Arg)基序的 8 倍重复组成。两种蛋白与 MHC 基因增强子中的 NF-kappa B 识别位点的结合亲和力明显高于与 kappa 免疫球蛋白基因增强子或 α1-抗胰蛋白酶基因启动子的 B 结构域的亲和力。 mRNA表达分析表明AT-BP1和AT-BP2在所有检查的组织中都有表达。虽然 AT-BP1 和 AT-BP2 的生理作用仍有待阐明,但它们预测的氨基酸序列及其 DNA 结合特征表明它们作为转录调节因子的作用。
Two partial cDNAs coding for DNA-binding proteins (AT-BP1 and AT-BP2) have been isolated. Both proteins, when prepared from lambda gt11 lysogens, bind to the B-domain of the alpha 1-antitrypsin promoter, an element which is important for the liver-specific expression of alpha 1-antitrypsin. Analysis of the cDNA sequences encoding these proteins reveals that both contain two zinc fingers of the Cys2-His2 type followed by a highly acidic stretch of 20 amino acids. AT-BP1 contains a second putative DNA-binding domain consisting of an 8-fold repeat of a SPKK (Ser-Pro-Lys/Arg-Lys/Arg) motif. Both proteins bind to the NF-kappa B recognition site in the MHC gene enhancer with significantly higher affinity than to the kappa immunoglobulin gene enhancer, or to the B-domain of the alpha 1-antitrypsin gene promoter. Analysis of mRNA expression shows that AT-BP1 and AT-BP2 are expressed in all the tissues examined. While the physiological roles of AT-BP1 and AT-BP2 remain to be elucidated, their predicted amino acid sequence and their DNA-binding characteristics suggest a role as transcriptional regulators.