{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:09:28Z","timestamp":1789132168867,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG 2550"],"award-info":[{"award-number":["RTG 2550"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Jo 187\/8-1"],"award-info":[{"award-number":["Jo 187\/8-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RTG 2550"],"award-info":[{"award-number":["RTG 2550"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Jo 187\/8-1"],"award-info":[{"award-number":["Jo 187\/8-1"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The interplay between the posttranslational modifiers SUMO and ubiquitin mediates the degradation of proteins. This crosstalk is conveyed by SUMO-targeted ubiquitin ligases (STUbLs). The best-studied STUbL in Saccharomyces cerevisiae is the heterodimer Slx5-Slx8 (Uls2). Uls2 mainly resides in the nucleus and is involved in stress tolerance, DNA repair and genome stability maintenance. So far, the majority of known Uls2 targets are nuclear proteins. The role of Uls2 in the targeting of cytosolic proteins remains to be elucidated. In this study, we identify Nis1 and Fir1 as two cytosolic proteins that become substrates of Uls2 in the absence of their partner polypeptides, which results in their SUMO-dependent aggregate formation in the nucleus. To uncover further Uls2 targets, we performed whole-cell proteomics of slx5\u0394 cells with and without oxidative stress. Comparison to wild-type cells revealed a large pool of potential Uls2 substrates, a subset of which is targeted upon oxidative stress, suggesting a quality control (QC) mechanism. Based on our results, we propose a role for Uls2 in a QC system targeting cytosolic proteins lacking their partners or that are damaged, for example, by oxidation.<\/jats:p>","DOI":"10.3390\/biom16091322","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:24:33Z","timestamp":1789129473000},"page":"1322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Nuclear SUMO-Targeted Ubiquitin Ligase Uls2 (Slx5-Slx8) in Quality Control of Cytosolic Proteins"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4202-5921","authenticated-orcid":false,"given":"Friederike","family":"Profe-Austermann","sequence":"first","affiliation":[{"name":"Center of Molecular Biosciences, Institute for Genetics, Department of Biology, Faculty of Natural Sciences and Mathematics, University of Cologne, 50674 Cologne, 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Biosciences, Institute for Genetics, Department of Biology, Faculty of Natural Sciences and Mathematics, University of Cologne, 50674 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9176-3830","authenticated-orcid":false,"given":"Maximilian","family":"Haka","sequence":"additional","affiliation":[{"name":"Center of Molecular Biosciences, Institute for Genetics, Department of Biology, Faculty of Natural Sciences and Mathematics, University of Cologne, 50674 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ganapathi","family":"Kandasamy","sequence":"additional","affiliation":[{"name":"Center of Molecular Biosciences, Institute for Genetics, Department of Biology, Faculty of Natural Sciences and Mathematics, University of Cologne, 50674 Cologne, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5846-6941","authenticated-orcid":false,"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 50674 Cologne, Germany"},{"name":"Center for Molecular Medicine (CMMC), University of Cologne, 50674 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5756-6780","authenticated-orcid":false,"given":"R. 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