A High-Confidence Interaction Map Identifies SIRT1 as a Mediator of Acetylation of USP22 and the SAGA Coactivator Complex
A High-Confidence Interaction Map Identifies SIRT1 as a Mediator of Acetylation of USP22 and the SAGA Coactivator Complex
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DOI：
10.1128/mcb.00971-12
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发表时间：
2013-04-01
影响因子：
5.3
通讯作者：
Sinclair, David A.
中科院分区：
文献类型：
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作者：
Armour, Sean M.;Bennett, Eric J.;Sinclair, David A.
尽管许多功能和靶点都归因于组蛋白和蛋白质去乙酰化酶SIRT1，但尚未建立对SIRT1结合蛋白的综合分析，从而产生高可信度的相互作用图。利用结合伙伴的比较统计分析，我们组装了一个高置信度的SIRT1相互作用组。利用这种方法，我们确定了去泛素化酶泛素特异性蛋白酶22 (USP22)，它是SAGA转录共激活复合体的去泛素化模块（DUBm）的一个组成部分，是sirt1相互作用的伙伴。我们发现这种相互作用是高度特异性的，需要USP22的ZnF-UBP结构域，并且被SIRT1内灭活的H363Y突变破坏。此外，我们发现USP22在多个赖氨酸残基上被乙酰化，并且在ZnF-UBP结构域中改变一个赖氨酸（K129）足以改变DUBm与核心SAGA复合物的相互作用。此外，usp22介导的SIRT1活性募集促进了单个SAGA复合物组分的去乙酰化。我们的研究结果表明sirt1介导的去乙酰化在调节较大的SAGA复合物中DUBm亚复合物的形成中起重要作用。
Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1, a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map has not been established. Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. Employing this method, we identified the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22), a component of the deubiquitinating module (DUBm) of the SAGA transcriptional coactivating complex, as a SIRT1-interacting partner. We found that this interaction is highly specific, requires the ZnF-UBP domain of USP22, and is disrupted by the inactivating H363Y mutation within SIRT1. Moreover, we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine (K129) within the ZnF-UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex. Furthermore, USP22-mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components. Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex.