Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks

Mol Cell Proteomics. 2012 Jul;11(7):M111.016162. doi: 10.1074/mcp.M111.016162. Epub 2012 Apr 5.


Ubiquitination controls the stability or function of many human proteins, thereby regulating a wide range of physiological processes. In most cases the combinatorial pattern of protein interactions that facilitate substrate recognition or modification remain unclear. Moreover, the efficiency of ubiquitination reactions can be altered by the formation of homo- and heterotypic E3-RING complexes. To establish the prevalence and nature of binary E3-RING/E3-RING interactions systematic yeast two-hybrid screens were performed to test 7269 potential interactions between 124 human E3-RING proteins. These studies identified 228 dimeric interactions between 100 E3-RINGs, of which 205 were novel. Complementary co-immunoprecipitation studies were performed to test predicted network interactions, showing a high correlation (64%) with primary yeast two-hybrid data. This data was integrated with known E3-RING interactions, tissue expression profiles and proteomic ubiquitination datasets to facilitate identification of subnetworks in which E3-RING dimerization events have the potential to alter network structure. These results reveal a widespread yet selective pattern of E3-RING dimerization events, which have the potential to confer further combinatorial complexity within human ubiquitination cascades.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dimerization
  • Humans
  • Immunoprecipitation
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Protein Binding
  • Protein Interaction Maps
  • Proteomics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Two-Hybrid System Techniques
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination*


  • Multiprotein Complexes
  • Ubiquitin
  • Ubiquitin-Protein Ligases