{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:12:49Z","timestamp":1790745169837,"version":"4.1.0"},"reference-count":25,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["340260 PalmERa"],"award-info":[{"award-number":["340260 PalmERa"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Many membrane proteins fold inefficiently and require the help of enzymes and chaperones. Here we reveal a novel folding assistance system that operates on membrane proteins from the cytosolic side of the endoplasmic reticulum (ER). We show that folding of the Wnt signaling coreceptor LRP6 is promoted by ubiquitination of a specific lysine, retaining it in the ER while avoiding degradation. Subsequent ER exit requires removal of ubiquitin from this lysine by the deubiquitinating enzyme USP19. This ubiquitination-deubiquitination is conceptually reminiscent of the glucosylation-deglucosylation occurring in the ER lumen during the calnexin\/calreticulin folding cycle. To avoid infinite futile cycles, folded LRP6 molecules undergo palmitoylation and ER export, while unsuccessfully folded proteins are, with time, polyubiquitinated on other lysines and targeted to degradation. This ubiquitin-dependent folding system also controls the proteostasis of other membrane proteins as CFTR and anthrax toxin receptor 2, two poor folders involved in severe human diseases.<\/jats:p>","DOI":"10.7554\/elife.19083","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T08:00:33Z","timestamp":1476777633000},"source":"Crossref","is-referenced-by-count":48,"title":["Ubiquitin-dependent folding of the Wnt signaling coreceptor LRP6"],"prefix":"10.7554","volume":"5","author":[{"given":"Elsa","family":"Perrody","sequence":"first","affiliation":[{"name":"Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Abrami","sequence":"additional","affiliation":[{"name":"Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Feldman","sequence":"additional","affiliation":[{"name":"Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Kunz","sequence":"additional","affiliation":[{"name":"Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Urb\u00e9","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8522-274X","authenticated-orcid":true,"given":"F Gisou","family":"van der Goot","sequence":"additional","affiliation":[{"name":"Global Health Institute, Ecole Polytechnique 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