BAZF, a novel Bcl6 homolog, functions as a transcriptional repressor

BAZF, a novel Bcl6 homolog, functions as a transcriptional repressor
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DOI:
10.1128/mcb.18.7.4235
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发表时间:
1998-07-01
影响因子:
5.3
通讯作者:
Tokuhisa, T
Tokuhisa, T
中科院分区:
生物学2区
文献类型:
--
作者:
Okabe, S;Fukuda, T;Tokuhisa, T

文献摘要

被引文献

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BCL 6基因是从B细胞淋巴瘤的染色体易位断裂点中鉴定出来的,其功能是序列特异性转录抑制因子。我们克隆了一个新的Bcl 6同源基因BAZF(编码Bcl 6相关锌指蛋白)。BAZF的氨基酸序列预测表明BTB/POZ结构域和Kruppel样锌指基序的5个重复序列分别位于NH端和COOH端。BAZF与Bcl 6在BTB/POZ结构域结合,定位于细胞核。由于BAZF的锌指基序与Bcl 6的锌指基序在氨基酸水平上有94%的相同性,因此BAZF特异性地结合Bcl 6的DNA结合序列,并作为转录抑制因子发挥作用。阻遏物活性与BTB/POZ结构域和BAZF中间部分相关。BAZF与Bcl 6之间的中间17个氨基酸的序列是完全保守的,并且保守的区域是阻遏物活性的关键区域。BAZF mRNA的表达,如Bcl 6 mRNA的表达,诱导在活化的淋巴细胞作为一个立即早期基因。因此,尽管BAZF的组织表达模式与Bcl 6不同,但BAZF的生化特征与Bcl 6相似。这显然是第一个报告的基因家族,其成员编码的锌指蛋白与BTB/POZ结构域。
The BCL6 gene, which has been identified from the chromosomal translocation breakpoint in B-cell lymphomas, functions as a sequence-specific transcriptional repressor. We cloned a novel Bcl6-homologous gene, BAZF (encoding Bcl6-associated zinc finger protein). The predicted amino acid sequence of BAZF indicated that the BTB/POZ domain and the five repeats of the Kruppel-like zinc finger motif are located in the NH, terminal region and the COOH-terminal region, respectively. BAZF associated with Bcl6 at the BTB/POZ domain and localized in the nucleus. Since zinc finger motifs of BAZF were 94% identical to those of Bcl6 at the amino acid level, BAZF bound specifically to the DNA-binding sequence of Bcl6 and functioned as a transcriptional repressor. The repressor activity was associated with both the BTB/POZ domain and the middle portion of BAZF. The 17-amino-acid sequence in the middle portion was completely conserved between BAZF and Bcl6, and the conserved region was critical for the repressor activity. Expression of BAZF mRNA, like that of Bcl6 mRNA, was induced in activated lymphocytes as an immediate-early gene. Therefore, the biochemical character of BAZF is similar to that of Bcl6 although the tissue expression pattern of BAZF differs from that of Bcl6. This is apparently the first report of a gene family whose members encode zinc finger proteins with the BTB/POZ domain.