Okazawa Hitoshi, Rich Tina, Chang Alex, Lin Xi, Waragai Masaaki, Kajikawa Masunori, Enokido Yasushi, Komuro Akihiko, Kato Seishi, Shibata Masao, Hatanaka Hiroshi, Mouradian M Maral, Sudol Marius, Kanazawa Ichiro
Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan.
Neuron. 2002 May 30;34(5):701-13. doi: 10.1016/s0896-6273(02)00697-9.
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.
PQBP-1是基于其与多聚谷氨酰胺序列的相互作用而被分离出来的。在本研究中，我们通过体外和体内试验表明，ataxin-1与PQBP-1之间的关联受到扩展的多聚谷氨酰胺序列的正向影响。在细胞系中，这两种分子之间的相互作用诱导凋亡性细胞死亡。作为这一现象的一种可能潜在机制，我们发现突变型ataxin-1增强了PQBP-1与RNA聚合酶II大亚基（Pol II）C末端结构域的结合。这降低了磷酸化Pol II的水平和转录水平。我们的结果提示PQBP-1参与1型脊髓小脑共济失调（SCA1）的病理过程，并支持多聚谷氨酰胺介导的病理过程以转录修饰为基础这一观点。
