{"acknowledgement":"We thank Snezhana Oliferenko, Hesso Farhan, Chris Dunworth, and Lukas A Huber for critically reading the manuscript, Ming Li, Peter Espenshade, Sebastien Leon, and Scott Emr for reagents, Bob Kaufmann for help in characterizing the Dsc2 L1 loop mutant. This research was funded in part by the Austrian Science Fund (FWF) (10.55776/P32161, 10.55776/P34907, 10.55776/DOC82 to DT, and 10.55776/P36187 to OS), by a Lipotype lipidomics excellence award (LEA 2019) to OS, by a Luxembourg National Research Fund (FNR): Grant #13571826 to YW, and by European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 847681 (to KRL). For open access purposes, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission.","date_published":"2024-12-01T00:00:00Z","DOAJ_listed":"1","month":"12","year":"2024","_id":"18522","article_processing_charge":"Yes","language":[{"iso":"eng"}],"publisher":"Springer Nature","OA_type":"gold","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Weyer Y, Schwabl SI, Tang X, et al. The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi. <i>Nature Communications</i>. 2024;15. doi:<a href=\"https://doi.org/10.1038/s41467-024-53676-6\">10.1038/s41467-024-53676-6</a>","chicago":"Weyer, Yannick, Sinead I. Schwabl, Xuechen Tang, Astha Purwar, Konstantin Siegmann, Angela Ruepp, Theresia Dunzendorfer-Matt, et al. “The Dsc Ubiquitin Ligase Complex Identifies Transmembrane Degrons to Degrade Orphaned Proteins at the Golgi.” <i>Nature Communications</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41467-024-53676-6\">https://doi.org/10.1038/s41467-024-53676-6</a>.","short":"Y. Weyer, S.I. Schwabl, X. Tang, A. Purwar, K. Siegmann, A. Ruepp, T. Dunzendorfer-Matt, M.A. Widerin, V. Niedrist, N.J.M. Mutsters, M.G. Tettamanti, S. Weys, B. Sarg, L. Kremser, K.R. Liedl, O. Schmidt, D. Teis, Nature Communications 15 (2024).","mla":"Weyer, Yannick, et al. “The Dsc Ubiquitin Ligase Complex Identifies Transmembrane Degrons to Degrade Orphaned Proteins at the Golgi.” <i>Nature Communications</i>, vol. 15, 9257, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41467-024-53676-6\">10.1038/s41467-024-53676-6</a>.","ista":"Weyer Y, Schwabl SI, Tang X, Purwar A, Siegmann K, Ruepp A, Dunzendorfer-Matt T, Widerin MA, Niedrist V, Mutsters NJM, Tettamanti MG, Weys S, Sarg B, Kremser L, Liedl KR, Schmidt O, Teis D. 2024. The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi. Nature Communications. 15, 9257.","ieee":"Y. Weyer <i>et al.</i>, “The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi,” <i>Nature Communications</i>, vol. 15. Springer Nature, 2024.","apa":"Weyer, Y., Schwabl, S. I., Tang, X., Purwar, A., Siegmann, K., Ruepp, A., … Teis, D. (2024). The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-024-53676-6\">https://doi.org/10.1038/s41467-024-53676-6</a>"},"pmid":1,"volume":15,"status":"public","date_updated":"2024-11-11T10:08:13Z","author":[{"full_name":"Weyer, Yannick","first_name":"Yannick","last_name":"Weyer"},{"first_name":"Sinead I.","full_name":"Schwabl, Sinead I.","last_name":"Schwabl"},{"full_name":"Tang, Xuechen","first_name":"Xuechen","last_name":"Tang"},{"last_name":"Purwar","full_name":"Purwar, Astha","first_name":"Astha"},{"first_name":"Konstantin","full_name":"Siegmann, Konstantin","last_name":"Siegmann"},{"full_name":"Ruepp, Angela","first_name":"Angela","last_name":"Ruepp"},{"last_name":"Dunzendorfer-Matt","full_name":"Dunzendorfer-Matt, Theresia","first_name":"Theresia"},{"last_name":"Widerin","full_name":"Widerin, Michael A.","first_name":"Michael A."},{"full_name":"Niedrist, Veronika","first_name":"Veronika","last_name":"Niedrist"},{"last_name":"Mutsters","first_name":"Noa J.M.","full_name":"Mutsters, Noa J.M."},{"first_name":"Maria G.","full_name":"Tettamanti, Maria G.","last_name":"Tettamanti"},{"full_name":"Weys, Sabine","first_name":"Sabine","id":"caffa136-9669-11ed-9092-ceac12ac9c05","last_name":"Weys"},{"full_name":"Sarg, Bettina","first_name":"Bettina","last_name":"Sarg"},{"first_name":"Leopold","full_name":"Kremser, Leopold","last_name":"Kremser"},{"last_name":"Liedl","full_name":"Liedl, Klaus R.","first_name":"Klaus R."},{"first_name":"Oliver","full_name":"Schmidt, Oliver","last_name":"Schmidt"},{"last_name":"Teis","first_name":"David","full_name":"Teis, David"}],"publication_identifier":{"eissn":["2041-1723"]},"scopus_import":"1","quality_controlled":"1","doi":"10.1038/s41467-024-53676-6","article_type":"original","external_id":{"pmid":["39461958"]},"publication":"Nature Communications","abstract":[{"lang":"eng","text":"The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be extracted by Cdc48 for endosome and Golgi associated proteasomal degradation (EGAD), while others will undergo ESCRT dependent vacuolar degradation. Some substrates are degraded by both, EGAD- or ESCRT pathways. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thereby preserves cellular membrane protein and lipid composition."}],"oa_version":"Published Version","department":[{"_id":"MaHe"}],"publication_status":"published","date_created":"2024-11-10T23:01:58Z","type":"journal_article","day":"01","article_number":"9257","title":"The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi","intvolume":"        15","OA_place":"publisher"}