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转录因子BACH1通过其新的可变剪接异构体被募集到细胞核中。

Transcription factor BACH1 is recruited to the nucleus by its novel alternative spliced isoform.

作者信息

Kanezaki R, Toki T, Yokoyama M, Yomogida K, Sugiyama K, Yamamoto M, Igarashi K, Ito E

机构信息

Department of Pediatrics, School of Medicine and Department of Biology, Faculty of Sciences, Hirosaki University, Hirosaki 036-8563, Japan.

出版信息

J Biol Chem. 2001 Mar 9;276(10):7278-84. doi: 10.1074/jbc.M004227200. Epub 2000 Nov 7.

DOI:10.1074/jbc.M004227200
PMID:11069897
Abstract

The transcription factor Bach1 is a member of a novel family of broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) basic region leucine zipper factors. Bach1 forms a heterodimer with MafK, a member of the small Maf protein family (MafF, MafG, and MafK), which recognizes the NF-E2/Maf recognition element, a cis-regulatory motif containing a 12-O-tetradecanoylphorbol-13-acetate-responsive element. Here we describe the gene structure of human BACH1, including a newly identified promoter and an alternatively RNA-spliced truncated form of BACH1, designated BACH1t, abundantly transcribed in human testis. The alternate splicing originated from the usage of a novel exon located 5.6 kilobase pairs downstream of the exon encoding the leucine zipper domain, and produced a protein that contained the conserved BTB/POZ, Cap'n collar, and basic region domains, but lacked the leucine zipper domain essential for NF-E2/Maf recognition element binding. Subcellular localization studies using green fluorescent protein as a reporter showed that full-length BACH1 localized to the cytoplasm, whereas BACH1t accumulated in the nucleus. Interestingly, coexpression of BACH1 and BACH1t demonstrated interaction between the molecules and the induction of nuclear import of BACH1. These results suggested that BACH1t recruits BACH1 to the nucleus through BTB domain-mediated interaction.

摘要

转录因子Bach1是一个由广泛复合体、tramtrack、bric-a-brac/痘病毒和锌指(BTB/POZ)碱性区域亮氨酸拉链因子组成的新家族的成员。Bach1与小Maf蛋白家族(MafF、MafG和MafK)的成员MafK形成异二聚体,该家族识别NF-E2/Maf识别元件,这是一种包含12-O-十四烷酰佛波醇-13-乙酸酯反应元件的顺式调控基序。在此,我们描述了人类BACH1的基因结构,包括一个新鉴定的启动子和一种经RNA可变剪接的BACH1截短形式,命名为BACH1t,它在人类睾丸中大量转录。这种可变剪接源于使用了一个位于编码亮氨酸拉链结构域的外显子下游5.6千碱基对处的新外显子,并产生了一种蛋白质,该蛋白质包含保守的BTB/POZ、Cap'n collar和碱性区域结构域,但缺乏对NF-E2/Maf识别元件结合至关重要的亮氨酸拉链结构域。使用绿色荧光蛋白作为报告基因的亚细胞定位研究表明,全长BACH1定位于细胞质,而BACH1t则在细胞核中积累。有趣的是,BACH1和BACH1t的共表达证明了分子间的相互作用以及BACH1核输入的诱导。这些结果表明,BACH1t通过BTB结构域介导的相互作用将BACH1招募到细胞核中。

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