SAGA-Dependent Histone H2Bub1 Deubiquitination Is Essential for Cellular Ubiquitin Balance during Embryonic Development.
SAGA-Dependent Histone H2Bub1 Deubiquitination Is Essential for Cellular Ubiquitin Balance during Embryonic Development.
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DOI：
10.3390/ijms23137459
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发表时间：
2022-07-05
影响因子：
5.6
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中科院分区：
文献类型：
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泛素（Ubiquitin，ub）是一种在真核细胞中广泛表达的高度保守的小分子蛋白。泛素化是由酶催化的翻译后修饰，其活化、缀合和连接ub至蛋白质。底物可以通过添加单个泛素分子（单泛素化）或通过缀合几个泛素（多泛素化）来修饰。Monoubiquitination作为一种信号标记来控制各种生物过程。ub的细胞和空间分布由ub连接酶和去泛素化酶（DUB）的相反活性决定，DUB从蛋白质中去除ub以产生游离ub。在哺乳动物细胞中，总组蛋白H2 B的1-2%是单偶联喹啉化的。佐贺（Spt Ada Gcn 5乙酰转移酶）是一种转录辅激活因子，其DUB模块从H2 Bub 1中去除ub。哺乳动物佐贺DUB模块具有四个亚基：ATXN 7、ATXN 7 L3、USP 22和ENY 2。缺乏DUB活性的Atxn 7 l3 −/−小鼠胚胎，H2 Bub 1滞留增加了5倍，并在妊娠中期死亡。有趣的是，缺乏ub编码基因Ubc的胚胎具有相似的表型。在这里，我们提供了一个当前的数据概述，表明Atxn 7 l3 −/−胚胎中染色质上的H2 Bub 1保留可能导致游离ub分布的不平衡。因此，我们推测，ATXN 7 L3的DUBs影响游离细胞的UB池在发展过程中。
Ubiquitin (ub) is a small, highly conserved protein widely expressed in eukaryotic cells. Ubiquitination is a post-translational modification catalyzed by enzymes that activate, conjugate, and ligate ub to proteins. Substrates can be modified either by addition of a single ubiquitin molecule (monoubiquitination), or by conjugation of several ubs (polyubiquitination). Monoubiquitination acts as a signaling mark to control diverse biological processes. The cellular and spatial distribution of ub is determined by the opposing activities of ub ligase enzymes, and deubiquitinases (DUBs), which remove ub from proteins to generate free ub. In mammalian cells, 1–2% of total histone H2B is monoubiquitinated. The SAGA (Spt Ada Gcn5 Acetyl-transferase) is a transcriptional coactivator and its DUB module removes ub from H2Bub1. The mammalian SAGA DUB module has four subunits, ATXN7, ATXN7L3, USP22, and ENY2. Atxn7l3−/− mouse embryos, lacking DUB activity, have a five-fold increase in H2Bub1 retention, and die at mid-gestation. Interestingly, embryos lacking the ub encoding gene, Ubc, have a similar phenotype. Here we provide a current overview of data suggesting that H2Bub1 retention on the chromatin in Atxn7l3−/− embryos may lead to an imbalance in free ub distribution. Thus, we speculate that ATXN7L3-containing DUBs impact the free cellular ub pool during development.
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影响因子：
16
作者：
Hao YH;Fountain MD Jr;Fon Tacer K;Xia F;Bi W;Kang SH;Patel A;Rosenfeld JA;Le Caignec C;Isidor B;Krantz ID;Noon SE;Pfotenhauer JP;Morgan TM;Moran R;Pedersen RC;Saenz MS;Schaaf CP;Potts PR
通讯作者：
Potts PR
DOI：
10.1038/nrd.2017.152
发表时间：
2018-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Harrigan JA;Jacq X;Martin NM;Jackson SP
通讯作者：
Jackson SP
影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T
影响因子：
1.2
作者：
Baptista, Tiago;Devys, Didier
通讯作者：
Devys, Didier
影响因子：
4.8
作者：
Daniel, JA;Torok, MS;Grant, PA
通讯作者：
Grant, PA