Identification of the full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor
Identification of the full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor
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DOI：
10.1006/mcne.2001.1004
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发表时间：
2001-07-01
影响因子：
3.5
通讯作者：
Pützer, BM
中科院分区：
文献类型：
--
作者：
Rega, S;Stiewe, T;Pützer, BM
亨廷顿病（HD）的神经变性与广泛表达的亨廷顿蛋白中的谷氨酰胺束延长有关。虽然致病机制仍然未知，但突变亨廷顿蛋白在大脑中的独特物理特性表明，包括亨廷顿蛋白相互作用蛋白在内的其他因素可能发挥特定作用。我们以前已经确定了一个DNA结合基序在近端E1 A启动子的腺病毒血清型12负责E1 A自动调节。在这里，我们确定了p231 HBP蛋白作为DNA结合因子，其C-末端部分最近已被表征为亨廷顿蛋白相互作用蛋白HYPB的未知功能。我们已经确定了全长cDNA序列，确定了支持其基因调控功能的几个结构域，并将HBP 231基因定位于染色体3p21.2-p21.3。我们的研究结果提供了一个有趣的亨廷顿蛋白和DNA结合因子之间的分子联系，暗示这种相互作用可能会导致参与HD发病机制的细胞基因表达的改变。
Neurodegeneration in Huntington's disease (HD) is associated with an elongated glutamine tract in the widely expressed huntingtin protein. Although the pathogenic mechanisms are still unknown, the distinct physical properties of mutant huntingtin in the brain suggest that other factors including huntingtin-interacting proteins might play a specific role. We have previously identified a DNA-binding motif in the proximal E1A promoter of adenovirus serotype 12 as responsible for E1A autoregulation. Here, we identified the p231HBP protein as a DNA-binding factor, the C-terminal portion of which has recently been characterized as the huntingtin-interacting protein HYPB of unknown function. We have determined the full-length cDNA sequence, identified several domains supporting its gene regulatory functions, and mapped the HBP231 gene to chromosome 3p21.2-p21.3. Our results provide an interesting molecular link between huntingtin and a DNA-binding factor, implicating that this interaction might result in the alteration of cellular gene expression involved in HD pathogenesis.