《生命科学》 2019, 31(8): 763-768

Ataxin-7蛋白在基因调控中的作用及与SCA7疾病的关系

洪钧烨1，2，胡红雨1*

(1 中国科学院生物化学与细胞生物学研究所，上海 200031；2 中国科学院大学，北京 100049)

摘　要：摘　要：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。

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

HONG Jun-Ye1，2， HU Hong-Yu1*

(1 Shanghai Institute of Biochemistry and Cell Biology， Chinese Academy of Sciences， Shanghai 200031， China; 2 University of Chinese Academy of Sciences， Beijing 100049， China)

Abstract: Abstract: 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.