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Mol Cell Proteomics. 2017 May;16(5):812-823. doi: 10.1074/mcp.M116.063719. Epub 2017 Mar 2.

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

Author information

1
From the ‡Biochemistry, Cellular and Molecular Biology Graduate Program.
2
§Solomon H. Snyder Department of Neuroscience.
3
¶Department of Pharmacology and Molecular Sciences.
4
‖Wilmer Eye Institute.
5
**Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
6
‡‡Center for High-Throughput Biology.
7
§Solomon H. Snyder Department of Neuroscience, sblack@jhmi.edu.
8
§§Institute for Cell Engineering.
9
¶¶Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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 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.

PMID:
28254775
PMCID:
PMC5417823
DOI:
10.1074/mcp.M116.063719
[Indexed for MEDLINE]
Free PMC Article

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