THE MOLECULAR-BASIS OF THE UNDULATED PAX-1 MUTATION
THE MOLECULAR-BASIS OF THE UNDULATED PAX-1 MUTATION
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DOI：
10.1016/0092-8674(91)90434-z
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发表时间：
1991-09-06
期刊：
影响因子：
64.5
通讯作者：
GRUSS, P
中科院分区：
文献类型：
--
作者：
CHALEPAKIS, G;FRITSCH, R;GRUSS, P
小鼠成对的box基因Pax-1与小鼠发育突变波状(Un)有关，后者在脊柱中表现出畸形。在un小鼠中，存在导致Pax-1配对结构域保守部分的Gly-Ser交换的点突变。在这里，我们证明了Pax-1编码一种具有转录激活特性的DNA结合蛋白。Pax-1蛋白的DNA结合特异性已经在凝胶位移分析中得到了广泛的分析，并结合结合干扰实验，定义了一个DNA结合核心基序。比较野生型和unPax-1蛋白的DNA结合特性表明，在配对结构域的第15位的Gly-Ser替换显著降低了unPax-1蛋白的DNA结合亲和力，并改变了其DNA结合特异性。这些结果破译了非突变的分子基础。
The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column. In un mice, a point mutation leading to a Gly-Ser exchange in a conserved part of the paired domain of Pax-1 is present. Here we show that Pax-1 encodes a DNA-binding protein with transcriptional activating properties. The DNA-binding specificity of the Pax-1 protein has been extensively analyzed in gel shift assays, and in conjunction with binding interference experiments, a DNA-binding core motif was defined. Comparison of the DNA-binding properties of wild-type and un Pax-1 proteins demonstrates that the Gly-Ser replacement at position 15 within the paired domain dramatically decreases the DNA-binding affinity of the un Pax-1 protein and alters its DNA-binding specificity. These results decipher the molecular basis of the un mutation.