Functional and dynamic gene expression profiling of polyglutamine

聚谷氨酰胺的功能和动态基因表达谱

• 批准号: 14370213
• 负责人: OKAZAWA Hitoshi
• 金额: $ 5.12万
• 依托单位: Tokyo Medical and Dental University (2003)Tokyo Metropolitan Organization for Medical Research (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370213/
• 关键词: POLYGLUTAMINE DISEASES; MEURODEGENTATION; PQBP-1; TRANSCRIPTION; NUCLEARFUNCTION; RNA POLYMERASE II

Polyglutamine diseases are caused by abnormal proteins containing an elongated polyglutamine tract sequence. It is generally believed that aggregation of the mutant proteins is essential for the pathology. However, molecular events induced by abnormal proteins during aggregation process are not fully elucidated. In this project, we applied genomics and proteomics to this question and investigated which genes and proteins are affected in expression. In brief, we found that different disease genes cause different gene and protein expression changes in a neuron type-specific manner. During the process, we found novel modifier genes of polyglutamine disease pathology, which could be used for the future development of molecular therapeutics.

多聚谷氨酰胺疾病是由含有长聚谷氨酰胺束序列的异常蛋白引起的。一般认为突变蛋白的聚集对病理是必要的。然而，异常蛋白在聚集过程中诱导的分子事件尚未完全阐明。在这个项目中，我们将基因组学和蛋白质组学应用于这个问题，研究哪些基因和蛋白质在表达中受到影响。简而言之，我们发现不同的疾病基因以神经元类型特异性的方式引起不同的基因和蛋白质表达变化。在此过程中，我们发现了新的多聚谷氨酰胺病病理修饰基因，可为未来分子治疗的发展提供参考。

项目成果

Okazawa H.: "Polyglutamine disease : a transcription disorder?"Cellular Molecular Life Sciences. 60. 1427-1439 (2003)

Okazawa H.：“多聚谷氨酰胺疾病：一种转录障碍？”细胞分子生命科学。

Busch A. et al.: "Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin : a potential mechanism for loss of huntingtin function in Huntington's disease."Journal of Biological Chemistry. 278. 41452-41461 (2003)

Busch A.等人：“突变亨廷顿蛋白促进野生型亨廷顿蛋白的纤维形成：亨廷顿病中亨廷顿蛋白功能丧失的潜在机制。”生物化学杂志。

Busch A, Engemann S, Lurz R, Okazawa H, Lehrach H, Wanker EE.: "Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin: a potential mechanism for loss of huntingtin function in Huntington's disease."J Biol Chem.. 278. 41452-41461 (2003)

Busch A、Engemann S、Lurz R、Okazawa H、Lehrach H、Wanker EE.：“突变型亨廷顿蛋白促进野生型亨廷顿蛋白的纤维形成：亨廷顿病中亨廷顿蛋白功能丧失的潜在机制。”J Biol Chem.. 278

Okazawa H. et al.: "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death"Neuron. 34. 701-713 (2002)

Okazawa H.等人：“突变ataxin-1和PQBP-1之间的相互作用影响转录和细胞死亡”神经元。

Hoshino M. et al.: "Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein."Journal of Neurochemistry. 87. 257-267 (2003)

Hoshino M. 等人：“表达突变亨廷顿蛋白的原代神经元中保留了组蛋白脱乙酰酶活性。”神经化学杂志。