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新型人 BTB/POZ 结构域锌指蛋白 ZBTB1 抑制 CRE 的转录活性。

Novel human BTB/POZ domain-containing zinc finger protein ZBTB1 inhibits transcriptional activities of CRE.

机构信息

Department of Biochemistry and Molecular Biology, Medical College, Soochow University, Suzhou 215123, China.

出版信息

Mol Cell Biochem. 2011 Nov;357(1-2):405-14. doi: 10.1007/s11010-011-0911-5. Epub 2011 Jun 25.

Abstract

BTB/POZ protein family plays a key role in many biological processes by regulating the transcriptional activities of some downstream genes. Here, we characterized the member of C(2)H(2) type zinc finger gene, Zinc finger and BTB domain containing 1 (ZBTB1). The complete sequence of ZBTB1 cDNA contains a 2142 bp open reading frame (ORF) and encodes a 713 amino acid protein with an N-terminal BTB/POZ domain that is similar to the same domain of other known transcription regulators and eight classical zinc finger C(2)H(2) motifs in the C-terminus. Subcellular localization analysis demonstrated that ZBTB1 was localized to the nucleus, forming dot-like structures. Transcriptional activity assays showed that ZBTB1 was a transcription repressor and overexpression of ZBTB1 in the COS7 cells reduced the transcriptional activities of cAMP response element (CRE). Further studies showed that the BTB domain and ZNF motifs of ZBTB1 may both be involved in this suppression. These results suggest that ZBTB1 protein may act as a transcription repressor in the activation of CREB and cAMP-mediated signal transduction pathways to mediate cellular functions.

摘要

BTB/POZ 蛋白家族通过调节一些下游基因的转录活性,在许多生物学过程中发挥着关键作用。在这里,我们对 C(2)H(2)型锌指基因成员 Zinc finger and BTB domain containing 1 (ZBTB1)进行了表征。ZBTB1 cDNA 的完整序列包含一个 2142bp 的开放阅读框(ORF),编码一个 713 个氨基酸的蛋白质,其 N 端具有 BTB/POZ 结构域,与其他已知转录调节剂的相同结构域相似,C 端具有 8 个经典的锌指 C(2)H(2)基序。亚细胞定位分析表明,ZBTB1 定位于细胞核,形成点状结构。转录活性测定表明,ZBTB1 是一种转录抑制剂,在 COS7 细胞中转录因子 ZBTB1 的过表达降低了 cAMP 反应元件(CRE)的转录活性。进一步的研究表明,ZBTB1 的 BTB 结构域和 ZNF 基序都可能参与这种抑制。这些结果表明,ZBTB1 蛋白可能作为转录抑制剂,在 CREB 的激活和 cAMP 介导的信号转导途径中发挥作用,从而介导细胞功能。

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