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首页> 外文期刊>Molecular and Cellular Biology >The Highly Conserved β-Hairpin of the Paired DNA-Binding Domain Is Required for Assembly of Pax-Ets Ternary Complexes
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The Highly Conserved β-Hairpin of the Paired DNA-Binding Domain Is Required for Assembly of Pax-Ets Ternary Complexes

机译:Pax-Ets三元复合物的组装需要成对的DNA结合域的高度保守的β-发夹。

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Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a β-hairpin structure, is a target of mutations in congenital disorders of mice and humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins of the Ets proto-oncogene family to bind a composite DNA site that is essential for efficient transcription of the early-B-cell-specificmb-1 promoter. Here, evidence is provided for specific interactions between Ets-1 and the amino-terminal subdomains of Pax proteins. By tethering deletion fragments of Pax-5 to a heterologous DNA-binding domain, we show that 73 amino acids (amino acids 12 to 84) of its amino-terminal subdomain can recruit the ETS domain of Ets-1 to bind the composite site. Furthermore, an amino acid (Gln22) within the highly conserved β-hairpin motif of Pax-5 is essential for efficient recruitment of Ets-1. The ability to recruit Ets proteins to bind DNA is a shared property of Pax proteins, as demonstrated by cooperative DNA binding of Ets-1 with sequences derived from the paired domains of Pax-2 and Pax-3. The strict conservation of sequences required for recruitment of Ets proteins suggests that Pax-Ets interactions are important for regulating transcription in diverse tissues during cellular differentiation.
机译:Pax家族转录因子通过配对结构域结合DNA。该结构域由两个螺旋-转-螺旋基序和一个β-发夹结构组成,是小鼠和人类先天性疾病中突变的目标。以前,我们表明Pax-5(B细胞特异性激活蛋白)募集了Ets原癌基因家族的蛋白,以结合复合DNA位点,这对于早期B细胞特异性转录有效转录是必不可少的。 mb-1 启动子。在这里,为Ets-1和Pax蛋白的氨基末端亚结构域之间的特定相互作用提供了证据。通过将Pax-5的缺失片段束缚到异源DNA结合结构域,我们显示其氨基末端亚结构域的73个氨基酸(12至84位氨基酸)可以募集Ets-1的ETS结构域来结合复合位点。此外,Pax-5高度保守的β-发夹基序内的氨基酸(Gln22)对于有效募集Ets-1是必不可少的。募集Ets蛋白质结合DNA的能力是Pax蛋白质的一个共同特性,如Ets-1与源自Pax-2和Pax-3配对结构域的序列的DNA协同结合所证明的。 Ets蛋白募集所需序列的严格保守性表明,Pax-Ets相互作用对于调节细胞分化过程中各种组织的转录非常重要。

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