Physiological and pathological functions of PQBP-1

在本项目中，我们分析了PQBP-1的生理和病理功能，它是我们发现的一种新的与聚谷氨酰胺序列结合的蛋白。首先，我们发现PQBP-1还与SCA1的致病基因产物ataxin-1相互作用，协同诱导转录抑制。PQBP-1和ataxin-1之间的相互作用抑制了转录，不是在包涵体中，而是在核基质中，这表明了一种新的发病机制。此外，我们的研究表明，这种相互作用导致RNA聚合酶II的磷酸化形式(=活性形式)减少。这些结果与PQBP-1转基因小鼠一起，将有助于理解这种类型的神经退行性疾病。

In this project, we have analyzed physiological and pathological functions of PQBP-1, which we found as a novel binding protein to the polyglutamine sequences. First, we found that PQBP-1 also interacts with ataxin-1, a causative gene product of SCA1, and induces transcriptional repression cooperatively. The interaction between PQBP-1 and ataxin-1 inhibits transcription not in the inclusion body but in the nuclear matrix, suggesting a new cascade of pathogenesis. Furthermore, our study showed that the interaction leads to reduction of phosphorylated form (=active form) of RNA polymerase II. These results, together with transgenic mouse of PQBP-1, will contribute for understanding this type of neurodegenerative diseases.