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Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex

机译:SUMO结合蛋白的全局分析确定SUMOylation是INO80染色质重塑复合体的关键调节剂

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摘要

SUMOylation is a critical regulator of a broad range of cellular processes, and is thought to do so in part by modulation of protein interaction. To comprehensively identify human proteins whose interaction is modulated by SUMOylation, we developed an in vitro binding assay using human proteome microarrays to identify targets of SUMO1 and SUMO2. We then integrated these results with protein SUMOylation and protein-protein interaction data to perform network motif analysis. We focused on a single network motif we termed a SUMOmodPPI (SUMO-modulated Protein-Protein Interaction) that included the INO80 chromatin remodeling complex subunits TFPT and INO80E. We validated the SUMO-binding activity of INO80E, and showed that TFPT is a SUMO substrate both in vitro and in vivo. We then demonstrated a key role for SUMOylation in mediating the interaction between these two proteins, both in vitro and in vivo. By demonstrating a key role for SUMOylation in regulating the INO80 chromatin remodeling complex, this work illustrates the power of bioinformatics analysis of large data sets in predicting novel biological phenomena.
机译:SUMOylation是广泛细胞过程的关键调节剂,被认为部分通过调节蛋白质相互作用来实现。为了全面鉴定相互作用被SUMOylation调节的人类蛋白质,我们开发了一种使用人类蛋白质组微阵列的体外结合测定法来鉴定SUMO1和SUMO2的靶标。然后,我们将这些结果与蛋白质SUMOylation和蛋白质-蛋白质相互作用数据进行整合,以进行网络基序分析。我们专注于称为SUMOmodPPI(SUMO调节的蛋白质-蛋白质相互作用)的单个网络基序,其中包括INO80染色质重塑复杂亚基TFPT和INO80E。我们验证了INO80E的SUMO结合活性,并表明TFPT在体外和体内都是SUMO底物。然后,我们证明了SUMOylation在介导这两种蛋白质在体外和体内的相互作用中的关键作用。通过证明SUMOylation在调节INO80染色质重塑复合体中的关键作用,这项工作说明了大数据集的生物信息学分析在预测新型生物现象中的作用。

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