Ataxin-7蛋白在基因调控中的作用及与SCA7疾病的关系

The role of ataxin-7 protein in gene regulation and its relationship with SCA7 disease

Ataxin-7(Atx7)蛋白是真核细胞SAGA(Spt-Ada-Gcn5 acetyltransferase)复合物中的重要组成亚基,能将其去泛素化模块锚定到整个复合物上并起到骨架支撑作用,进而参与SAGA复合物对染色质组蛋白乙酰化和去泛素化修饰的调控。Atx7通过调控SAGA复合物与视锥视杆细胞同源盒基因蛋白(cone-rod homeobox,CRX)的结合,对依赖CRX的基因转录激活起到调节作用。然而,Atx7的N-端多聚谷氨酰胺(polyglutamine,PolyQ)序列的异常延伸,会使其在细胞内发生蛋白质积聚(aggregation),进而引起Ⅶ-型脊髓小脑共济失调症(spinocerebellar ataxia 7,SCA7)的发生。现综述Atx7在细胞内的正常生理功能及其PolyQ延伸引起的蛋白质积聚,探讨PolyQ延伸的Atx7对细胞功能的影响,以及最终引发神经退行性疾病的分子机制。

Ataxin-7(Atx7)is an important subunit of SAGA(Spt-Ada-Gcn5 acetyltransferase)complex in eukaryotic cells.It can help deubiquitination module(DUBm)anchor to the whole SAGA complex,and thus plays a role in transcriptional regulation through acetylation and deubiquitination of chromatin histones.Atx7 participates in the cone-rod homeobox(CRX)-dependent gene transcriptional activation by regulating the combination of SAGA with the CRX protein.However,expansion of the N-terminal polyglutamine(PolyQ)sequence of Atx7 will lead to protein aggregation in cells and thus spinocerebellar ataxia 7(SCA7).This article briefly introduces the physiological function of Atx7 in cells and the protein aggregation caused by PolyQ expansion,and then discusses the effect of PolyQ-expanded Atx7 on cellular function,as well as the pathogenic mechanism of neurodegenerative diseases.