Interaction between mutant ataxin-1 and POBP-1 affects transcription and cell death
Interaction between mutant ataxin-1 and POBP-1 affects transcription and cell death
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DOI：
10.1016/s0896-6273(02)00697-9
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发表时间：
2002-05-30
期刊：
影响因子：
16.2
通讯作者：
Kanazawa, I
中科院分区：
文献类型：
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作者：
Okazawa, H;Rich, T;Kanazawa, I
根据PQBP-1与聚谷氨酰胺束的相互作用分离得到PQBP-1。在这项研究中，通过体外和体内实验，我们发现ataxin-1和PQBP-1之间的关联受到扩展的聚谷氨酰胺序列的积极影响。在细胞系中，两种分子之间的相互作用诱导凋亡细胞死亡。作为这种现象的可能机制，我们发现突变体ataxin-1增强了PQBP-1与RNA聚合酶II大亚基（Pol II） c端结构域的结合。这降低了磷酸化的Pol II和转录水平。我们的研究结果表明PQBP-1参与脊髓小脑性共济失调1型（SCA1）的病理，并支持了转录修饰在多谷氨酰胺介导的病理基础上的观点。
PQBP-1 was isolated on the basis of its interaction with polyglutamine tracts. In this study, using in vitro and in vivo assays, we show that the association between ataxin-1 and PQBP-1 is positively influenced by expanded polyglutamine sequences. In cell lines, interaction between the two molecules induces apoptotic cell death. As a possible mechanism underlying this phenomenon, we found that mutant ataxin-1 enhances binding of PQBP-1 to the C-terminal domain of RNA polymerase II large subunit (Pol II). This reduces the level of phosphorylated Pol II and transcription. Our results suggest the involvement of PQBP-1 in the pathology of spinocerebellar ataxia type 1 (SCA1) and support the idea that modified transcription underlies polyglutamine-mediated pathology.