In vivo identification of human small ubiquitin-like modifier polymerization sites by high accuracy mass spectrometry and an in vitro to in vivo strategy

Mol Cell Proteomics. 2008 Jan;7(1):132-44. doi: 10.1074/mcp.M700173-MCP200. Epub 2007 Oct 15.

Abstract

The length and precise linkage of polyubiquitin chains is important for their biological activity. Although other ubiquitin-like proteins have the potential to form polymeric chains their identification in vivo is challenging and their functional role is unclear. Vertebrates express three small ubiquitin-like modifiers, SUMO-1, SUMO-2, and SUMO-3. Mature SUMO-2 and SUMO-3 are nearly identical and contain an internal consensus site for sumoylation that is missing in SUMO-1. Combining state-of-the-art mass spectrometry with an "in vitro to in vivo" strategy for post-translational modifications, we provide direct evidence that SUMO-1, SUMO-2, and SUMO-3 form mixed chains in cells via the internal consensus sites for sumoylation in SUMO-2 and SUMO-3. In vitro, the chain length of SUMO polymers could be influenced by changing the relative amounts of SUMO-1 and SUMO-2. The developed methodology is generic and can be adapted for the identification of other sumoylation sites in complex samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Extracts
  • Cell Nucleus / metabolism
  • HeLa Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mass Spectrometry
  • Molecular Sequence Data
  • Peptides / chemistry
  • Polymers / chemistry*
  • SUMO-1 Protein / chemistry
  • SUMO-1 Protein / isolation & purification
  • SUMO-1 Protein / metabolism
  • Small Ubiquitin-Related Modifier Proteins / chemistry*
  • Small Ubiquitin-Related Modifier Proteins / isolation & purification
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Ubiquitins / chemistry
  • Ubiquitins / isolation & purification
  • Ubiquitins / metabolism

Substances

  • Cell Extracts
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Peptides
  • Polymers
  • SUMO-1 Protein
  • SUMO2 protein, human
  • SUMO3 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitins