Premium
Conserved function of RNF4 family proteins in eukaryotes: targeting a ubiquitin ligase to SUMOylated proteins
Author(s) -
Sun Huaiyu,
Leverson Joel D,
Hunter Tony
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601839
Subject(s) - rnf4 , ubiquitin ligase , sumo protein , ubiquitin , ddb1 , microbiology and biotechnology , biology , ring finger domain , ubiquitin conjugating enzyme , ring finger , ubiquitin protein ligases , dna ligase , schizosaccharomyces , genetics , zinc finger , schizosaccharomyces pombe , transcription factor , mutant , dna , gene
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.