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PMID: 17762864 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The EMBO journal ·Vol. 26 ·No. 18 ·2007-09-19 ·Pages 4102-12

Sun H, Leverson JD, Hunter T

Abstract

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.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Animals Carrier Proteins/chemistry,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,genetics,metabolism Schizosaccharomyces pombe Proteins/chemistry,metabolism Sequence Homology, Amino Acid Small Ubiquitin-Related Modifier Proteins/metabolism Transcription Factors/metabolism Ubiquitin/metabolism Ubiquitin-Protein Ligases/metabolism
Chemicals
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
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sun Huaiyu
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Leverson Joel D
Hunter Tony
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601839
Published
2007-09-19
Epub
2007-00-30
Pages
4102-12
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2230674
Subset
IM
Grants
NCI NIH HHS · R01 CA080100 · United States
NCI NIH HHS · R01 CA082683 · United States
NCI NIH HHS · CA80100 · United States
NCI NIH HHS · CA82683 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7601839 PMC Full Text View journal details
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