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| EMBO J. Sep (2007); 26(18):4089-101 | |
| SUMO-targeted ubiquitin ligases in genome stability- | |
| Prudden J, Pebernard S, Raffa G, Slavin DA, Perry JJ, Tainer JA, McGowan CH, Boddy MN | |
| Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA- | |
| Abstract: We identify the SUMO-Targeted Ubiquitin Ligase -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- | |
| [PUBMED: 17762865] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |