SAGA (Spt-Ada-Gcn5-Acetyltransferase)是真核生物中一种具有进化保守性的转录共激活剂，是一个大型多亚基蛋白复合物，具有两种不同的酶活性，即组蛋白乙酰转移酶（HAT）和去泛素化酶（DUB）。它由基因特异性激活蛋白靶向到启动子，用于组蛋白共价修饰和预初始化复合物（PIC）形成，以增强转录（或基因激活）。SAGA靶向到基因启动子还进一步依赖于26S蛋白酶体的19S RP（调控粒子），19S RP参与有针对性的蛋白质降解通过泛素化的方式，但这种靶向过程与蛋白质降解无关。此外，最近发现SAGA还通过Sgf73/ataxin-7组分的泛素化依赖性蛋白质降解来调控26S蛋白酶体，Sgf73/ataxin-7是SAGA完整性和DUB活性（从而调控转录）所必需的组分，并与多种疾病，包括神经退行性疾病和癌症相关。因此，SAGA本身及其对活性基因的靶向受到泛素质子体系（UPS）的调控，与疾病有关。版权所有 © 2023 Elsevier B.V.发布.

SAGA (Spt-Ada-Gcn5-Acetyltransferase), an evolutionarily conserved transcriptional co-activator among eukaryotes, is a large multi-subunit protein complex with two distinct enzymatic activities, namely HAT (Histone acetyltransferase) and DUB (De-ubiquitinase), and is targeted to the promoter by the gene-specific activator proteins for histone covalent modifications and PIC (Pre-initiation complex) formation in enhancing transcription (or gene activation). Targeting of SAGA to the gene promoter is further facilitated by the 19S RP (Regulatory particle) of the 26S proteasome (that is involved in targeted degradation of protein via ubiquitylation) in a proteolysis-independent manner. Moreover, SAGA is also recently found to be regulated by the 26S proteasome in a proteolysis-dependent manner via the ubiquitylation of its Sgf73/ataxin-7 component that is required for SAGA's integrity and DUB activity (and hence transcription), and is linked to various diseases including neurodegenerative disorders and cancer. Thus, SAGA itself and its targeting to the active gene are regulated by the UPS (Ubiquitin-proteasome system) with implications in diseases.Copyright © 2023. Published by Elsevier B.V.