The Highly Conserved β-Hairpin of the Paired DNA-Binding Domain Is Required for Assembly of Pax-Ets Ternary Complexes
The Highly Conserved β-Hairpin of the Paired DNA-Binding Domain Is Required for Assembly of Pax-Ets Ternary Complexes
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Pax-Ets 三元复合物的组装需要配对 DNA 结合结构域的高度保守的 β-发夹
DOI：
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发表时间：
1999
影响因子：
5.3
通讯作者：
J. Hagman
中科院分区：
文献类型：
--
作者：
W. Wheat;D. Fitzsimmons;Heidi Lennox;Susan R. Krautkramer;L. Gentile;L. McIntosh;J. Hagman
摘要Pax家族转录因子通过配对结构域与DNA结合。该结构域由两个螺旋-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突变的靶点。在此之前，我们发现Pax-5(B细胞特异性激活蛋白)招募ETS原癌基因家族的蛋白质来结合一个复合DNA位点，这对于早期B细胞特异性mb-1启动子的高效转录是必不可少的。在这里，提供了Ets-1与Pax蛋白氨基末端亚域之间的特异性相互作用的证据。通过将Pax-5的缺失片段连接到一个异源DNA结合区，我们发现其氨基末端亚区的73个氨基酸(氨基酸12到84)可以招募Ets-1的Ets结构域与复合位点结合。此外，高度保守的β-发夹基序中的一个氨基酸(Gln22)对于Ets-1的有效招募是必不可少的。招募Ets蛋白与DNA结合的能力是Pax蛋白的共同特性，Ets-1与来自Pax-2和Pax-3的配对结构域的序列的协同DNA结合证明了这一点。ETS蛋白募集所需序列的严格保守性表明，在细胞分化过程中，Pax-ETS相互作用对于调节不同组织的转录是重要的。
ABSTRACT 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.
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影响因子：
10.5
作者：
Sander, M;Neubuser, A;German, MS
通讯作者：
German, MS
花斑症、瓦登堡综合征以及黑素细胞发育的相关疾病。
DOI：
10.1016/s1085-5629(97)80031-4
发表时间：
1997
期刊：
Seminars in cutaneous medicine and surgery.
影响因子：
--
作者：
Spritz,RA
通讯作者：
Spritz,RA
影响因子：
10.5
作者：
EPSTEIN, JA;GLASER, T;MAAS, RL
通讯作者：
MAAS, RL
影响因子：
10.5
作者：
Fitzsimmons, D;Hodsdon, W;Hagman, J
通讯作者：
Hagman, J
影响因子：
10.5
作者：
Brass, AL;Kehrli, E;Singh, H
通讯作者：
Singh, H