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首页> 外文期刊>Molecular & cellular proteomics: MCP >Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex
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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将Sumoylative作为INO80染色质重塑复合物的关键调节器

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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是广泛的细胞过程的关键调节因子，并且被认为是通过调制蛋白质相互作用的部分。为了全面鉴定其相互作用的蛋白质通过Sublation调节的蛋白质，我们使用人蛋白质组微阵列开发了体外结合测定以鉴定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，以进行网络图案分析。我们专注于单一网络基序，我们称之为SUMOMODPPP（SUMO调制的蛋白质 - 蛋白质相互作用），其包括INO80染色质重塑复合亚基TFPT和INO80e。我们验证了Ino80e的SUMO结合活性，并显示TFPT是体外和体内的SUMO底物。然后，我们向Sumoylation介绍了在体外和体内介导这两种蛋白质之间的相互作用的关键作用。通过证明Sublation在调节InO80染色质重塑复合物中的突起中的关键作用，这项工作说明了在预测新的生物现象中的大数据集的生物信息学分析的力量。

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    Cox Eric; Hwang Woochang; Uzoma Ijeoma; Hu Jianfei; Guzzo Catherine M.; Jeong Junseop; Matunis Michael J.; Qian Jiang; Zhu Heng; Blackshaw Seth;

  • 作者单位

    Johns Hopkins Univ Sch Med Biochem Cellular &

    Mol Biol Grad Program Baltimore MD USA;

    Johns Hopkins Univ Sch Med Wilmer Eye Inst Baltimore MD 21205 USA;

    Johns Hopkins Univ Sch Med Dept Pharmacol &

    Mol Sci Baltimore MD 21205 USA;

    Johns Hopkins Univ Sch Med Wilmer Eye Inst Baltimore MD 21205 USA;

    Johns Hopkins Univ Bloomberg Sch Publ Hlth Dept Biochem &

    Mol Biol Baltimore MD USA;

    Johns Hopkins Univ Sch Med Dept Pharmacol &

    Mol Sci Baltimore MD 21205 USA;

    Johns Hopkins Univ Bloomberg Sch Publ Hlth Dept Biochem &

    Mol Biol Baltimore MD USA;

    Johns Hopkins Univ Sch Med Wilmer Eye Inst Baltimore MD 21205 USA;

    Johns Hopkins Univ Sch Med Dept Pharmacol &

    Mol Sci Baltimore MD 21205 USA;

    Johns Hopkins Univ Sch Med Solomon H Snyder Dept Neurosci Baltimore MD USA;

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  • 正文语种 eng
  • 中图分类 生物化学;
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