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SUMO‐targeted ubiquitin ligases in genome stability
Author(s) -
Prudden John,
Pebernard Stephanie,
Raffa Grazia,
Slavin Daniela A,
Perry J Jefferson P,
Tainer John A,
McGowan Clare H,
Boddy Michael N
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.7601838
Subject(s) - sumo protein , biology , ubiquitin ligase , schizosaccharomyces , ubiquitin , rnf4 , schizosaccharomyces pombe , sumo enzymes , microbiology and biotechnology , saccharomyces cerevisiae , genetics , dna repair , ubiquitin protein ligases , dna ligase , genome instability , dna damage , transcription factor , dna , zinc finger , gene
We identify the S UMO‐ T argeted Ub iquitin L igase (STUbL) family of proteins and propose that STUbLs selectively ubiquitinate sumoylated proteins and proteins that contain SUMO‐like domains (SLDs). STUbL recruitment to sumoylated/SLD proteins is mediated by tandem SUMO interaction motifs (SIMs) within the STUbLs N‐terminus. STUbL‐mediated ubiquitination maintains sumoylation pathway homeostasis by promoting target protein desumoylation and/or degradation. Thus, STUbLs establish a novel mode of communication between the sumoylation and ubiquitination pathways. STUbLs are evolutionarily conserved and include: Schizosaccharomyces pombe Slx8‐Rfp (founding member), Homo sapiens RNF4, Dictyostelium discoideum MIP1 and Saccharomyces cerevisiae Slx5–Slx8. Cells lacking Slx8‐Rfp accumulate sumoylated proteins, display genomic instability, and are hypersensitive to genotoxic stress. These phenotypes are suppressed by deletion of the major SUMO ligase Pli1, demonstrating the specificity of STUbLs as regulators of sumoylated proteins. Notably, human RNF4 expression restores SUMO pathway homeostasis in fission yeast lacking Slx8‐Rfp, underscoring the evolutionary functional conservation of STUbLs. The DNA repair factor Rad60 and its human homolog NIP45, which contain SLDs, are candidate STUbL targets. Consistently, Rad60 and Slx8‐Rfp mutants have similar DNA repair defects.