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| J. Biol. Chem. Nov (2007); 282(47):34167-75 | |
| Ubiquitin-dependent proteolytic control of SUMO conjugates- | |
| Uzunova K, Gottsche K, Miteva M, Weisshaar SR, Glanemann C, Schnellhardt M, Niessen M, Scheel H, Hofmann K, Johnson ES, Praefcke GJ, Dohmen RJ | |
| Institute for Genetics, University of Cologne, Zulpicher Strasse 47, Cologne, Germany- | |
| Abstract: Posttranslational protein modification with small ubiquitin-related modifier -SUMO- is an important regulatory mechanism implicated in many cellular processes, including several of biomedical relevance- We report that inhibition of the proteasome leads to accumulation of proteins that are simultaneously conjugated to both SUMO and ubiquitin in yeast and in human cells- A similar accumulation of such conjugates was detected in Saccharomyces cerevisiae ubc4 ubc5 cells as well as in mutants lacking two RING finger proteins, Ris1 and Hex3-Slx5-Slx8, that bind to SUMO as well as to the ubiquitin-conjugating enzyme Ubc4- In vitro, Hex3-Slx8 complexes promote Ubc4-dependent ubiquitylation- Together these data identify a previously unrecognized pathway that mediates the proteolytic down-regulation of sumoylated proteins- Formation of substrate-linked SUMO chains promotes targeting of SUMO-modified substrates for ubiquitin-mediated proteolysis- Genetic and biochemical evidence indicates that SUMO conjugation can ultimately lead to inactivation of sumoylated substrates by polysumoylation and-or ubiquitin-dependent degradation- Simultaneous inhibition of both mechanisms leads to severe phenotypic defects- | |
| [PUBMED: 17728242] |   |
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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. |