Poly-small ubiquitin-like modifier (PolySUMO)-binding proteins identified through a string search

J Biol Chem. 2012 Dec 7;287(50):42071-83. doi: 10.1074/jbc.M112.410985. Epub 2012 Oct 18.

Abstract

Polysumoylation is a crucial cellular response to stresses against genomic integrity or proteostasis. Like the small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase RNF4, proteins with clustered SUMO-interacting motifs (SIMs) can be important signal transducers downstream of polysumoylation. To identify novel polySUMO-binding proteins, we conducted a computational string search with a custom Python script. We found clustered SIMs in another RING domain protein Arkadia/RNF111. Detailed biochemical analysis of the Arkadia SIMs revealed that dominant SIMs in a SIM cluster often contain a pentameric VIDLT ((V/I/L/F/Y)(V/I)DLT) core sequence that is also found in the SIMs in PIAS family E3s and is likely the best-fitted structure for SUMO recognition. This idea led to the identification of additional novel SIM clusters in FLASH/CASP8AP2, C5orf25, and SOBP/JXC1. We suggest that the clustered SIMs in these proteins form distinct SUMO binding domains to recognize diverse forms of protein sumoylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Animals
  • HEK293 Cells
  • Humans
  • Mice
  • Nuclear Proteins* / genetics
  • Nuclear Proteins* / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • SUMO-1 Protein* / genetics
  • SUMO-1 Protein* / metabolism
  • Sequence Analysis, Protein*
  • Sumoylation / physiology*
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitin-Protein Ligases* / metabolism

Substances

  • Nuclear Proteins
  • SUMO-1 Protein
  • RNF111 protein, human
  • Rnf111 protein, mouse
  • Ubiquitin-Protein Ligases