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

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

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.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Chromatin Assembly and Disassembly*
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • Gene Ontology
  • Humans
  • Lysine / metabolism
  • Molecular Chaperones / metabolism
  • Protein Array Analysis
  • Protein Binding
  • Protein Domains
  • Protein Inhibitors of Activated STAT / metabolism
  • Protein Interaction Maps
  • Proteome / metabolism
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Sumoylation*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Molecular Chaperones
  • PIAS1 protein, human
  • PIAS3 protein, human
  • Protein Inhibitors of Activated STAT
  • Proteome
  • Small Ubiquitin-Related Modifier Proteins
  • TFPT protein, human
  • DNA Helicases
  • INO80 protein, human
  • Lysine

Associated data

  • PDB/2PE6
  • PDB/4BKG