Physiological and pathological functions of PQBP-1

PQBP-1的生理和病理功能

• 批准号: 12670596
• 负责人: OKAZAWA Hitoshi
• 金额: $ 2.11万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670596/
• 关键词: PQBP-1; polyglutamine; transcription; cell death; neuron; spinocerebellar degeneration; ポリグルタミン; 神経細胞死; U5-15kD; スプライシング; スプライミング

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.

在本项目中，我们分析了PQBP-1的生理和病理功能，这是我们发现的一个新的结合蛋白的多聚谷氨酰胺序列。首先，我们发现PQBP-1也与SCA 1的致病基因产物ataxin-1相互作用，并协同诱导转录抑制。PQBP-1和共济失调蛋白-1之间的相互作用抑制转录不是在包涵体，但在核基质，这表明一个新的级联的发病机制。此外，我们的研究表明，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转基因小鼠的研究结果将有助于对这类神经退行性疾病的认识。

项目成果

Shoji M. et al.: "JNK activation is associated with intracellular β-amyloid accumulation."Molecular Brain Research. 85. 221-223 (2001)

Shoji M. 等人：“JNK 激活与细胞内 β-淀粉样蛋白积累相关。”《分子脑研究》85. 221-223 (2001)。

Ueda H, Goto J, Hashida H, Lin X, Oyanagi K, kawano H, et al.: "Enhanced SUMOylation in polyglutamine diseases"Biochem. Biophys. Res. Commun.. (in press).

Ueda H、Goto J、Hashida H、Lin X、Oyanagi K、kawano H 等：“多谷氨酰胺疾病中增强的 SUMO 化”Biochem。

Ueda H., Goto J., Hashida H., Lin X., Oyanagi K., Kawano H., Zoghbi H.Y., Kanazawa I., and Okazawa H.: "Enhanced SUMOylation in polyglutamine diseases."Biochem. Biophys. Res. Commun.. (in press). (2002)

Ueda H.、Goto J.、Hashida H.、Lin X.、Oyanagi K.、Kawano H.、Zoghbi H.Y.、Kanazawa I. 和 Okazawa H.：“多谷氨酰胺疾病中增强的 SUMOylation。”Biochem。

Waragai M. et al.: "PQBP-1/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5-15KD/dim1p via the Carboxyl-terminal domain."Biochem.Biophys.Res.Commun.. 273. 592-595 (2000)

Waragai M. 等人：“PQBP-1/Npw38 是一种与聚谷氨酰胺束结合的核蛋白，通过羧基末端结构域与 U5-15KD/dim1p 相互作用。”Biochem.Biophys.Res.Commun.. 273. 592

Shoji M., Iwakami N., Takeuchi S., Waragai M., Suzuki M., Kanazawa M., Lippa C.F., Ono S. and Okazawa H.: "JNK activation is associated with intracellular beta-amyloid accumulation."Molecular Brain Research. 85. 221-233 (2000)

Shoji M.、Iwakami N.、Takeuchi S.、Waragai M.、Suzuki M.、Kanazawa M.、Lippa C.F.、Ono S. 和 Okazawa H.：“JNK 激活与细胞内 β-淀粉样蛋白积累相关。”《分子脑》