Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins

EMBO J. 2007 Sep 19;26(18):4102-12. doi: 10.1038/sj.emboj.7601839. Epub 2007 Aug 30.


The function of small ubiquitin-like modifier (SUMO)-binding proteins is key to understanding how SUMOylation regulates cellular processes. We identified two related Schizosaccharomyces pombe proteins, Rfp1 and Rfp2, each having an N-terminal SUMO-interacting motif (SIM) and a C-terminal RING-finger domain. Genetic analysis shows that Rfp1 and Rfp2 have redundant functions; together, they are essential for cell growth and genome stability. Mammalian RNF4, an active ubiquitin E3 ligase, is an orthologue of Rfp1/Rfp2. Rfp1 and Rfp2 lack E3 activity but recruit Slx8, an active RING-finger ubiquitin ligase, through a RING-RING interaction, to form a functional E3. RNF4 complements the growth and genomic stability defects of rfp1rfp2, slx8, and rfp1rfp2slx8 mutant cells. Both the Rfp-Slx8 complex and RNF4 specifically ubiquitylate artificial SUMO-containing substrates in vitro in a SUMO binding-dependent manner. SUMOylated proteins accumulate in rfp1rfp2 double-null cells, suggesting that Rfp/Slx8 proteins may promote ubiquitin-dependent degradation of SUMOylated targets. Hence, we describe a family of SIM-containing RING-finger proteins that potentially regulates eukaryotic genome stability through linking SUMO-interaction with ubiquitin conjugation.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Eukaryotic Cells / metabolism*
  • Evolution, Molecular*
  • Genomic Instability
  • Mice
  • Molecular Sequence Data
  • Multigene Family*
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Transport
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism*


  • Carrier Proteins
  • Cell Cycle Proteins
  • Nuclear Proteins
  • Rpf1 protein, S pombe
  • Rpf2 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Ubiquitin
  • Rnf4 protein, mouse
  • Slx8 protein, S pombe
  • Ubiquitin-Protein Ligases