title: Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex.
abstract: 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 anin vitrobinding 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 bothin vitroandin vivoWe then demonstrated a key role for SUMOylation in mediating the interaction between these two proteins, bothin vitroandin vivoBy 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.
authors.affiliation: From the ‡Biochemistry, Cellular and Molecular Biology Graduate Program.|§Solomon H. Snyder Department of Neuroscience.|¶Department of Pharmacology and Molecular Sciences.
authors.forename: Eric
authors.initials: E
authors.lastname: Cox
authors.affiliation: ‖Wilmer Eye Institute.
authors.forename: Woochang
authors.initials: W
authors.lastname: Hwang
authors.affiliation: ¶Department of Pharmacology and Molecular Sciences.
authors.forename: Ijeoma
authors.initials: I
authors.lastname: Uzoma
authors.affiliation: ‖Wilmer Eye Institute.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Hu
authors.affiliation: **Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Guzzo
authors.affiliation: ¶Department of Pharmacology and Molecular Sciences.|‡‡Center for High-Throughput Biology.
authors.forename: Junseop
authors.initials: J
authors.lastname: Jeong
authors.affiliation: **Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Matunis
authors.affiliation: ‖Wilmer Eye Institute.
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.affiliation: ¶Department of Pharmacology and Molecular Sciences.|‡‡Center for High-Throughput Biology.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: §Solomon H. Snyder Department of Neuroscience, sblack@jhmi.edu.|‡‡Center for High-Throughput Biology.|§§Institute for Cell Engineering.|¶¶Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins; D063990:Gene Ontology; D006801:Humans; D008239:Lysine / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D040081:Protein Array Analysis; D011485:Protein Binding; D000072417:Protein Domains; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D051792:Basic Helix-Loop-Helix Proteins; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D008239:Lysine; D018832:Molecular Chaperones; D050828:Protein Inhibitors of Activated STAT; D020543:Proteome; D025841:Small Ubiquitin-Related Modifier Proteins; C106529:PIAS1 protein, human; C484745:PIAS3 protein, human; C118089:TFPT protein, human; C524421:INO80 protein, human