{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:18:12Z","timestamp":1791951492379,"version":"4.3.4"},"reference-count":57,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,3,7]]},"abstract":"<jats:p>The Hedgehog (Hh) signaling pathway has important functions during metazoan development. The Hh ligand is generated from a precursor by self-cleavage, which requires a free cysteine in the C-terminal part of the protein and results in the production of the cholesterol-modified ligand and a C-terminal fragment. In this paper, we demonstrate that these reactions occur in the endoplasmic reticulum (ER). The catalytic cysteine needs to form a disulfide bridge with a conserved cysteine, which is subsequently reduced by protein disulfide isomerase. Generation of the C-terminal fragment is followed by its ER-associated degradation (ERAD), providing the first example of an endogenous luminal ERAD substrate that is constitutively degraded. This process requires the ubiquitin ligase Hrd1, its partner Sel1, the cytosolic adenosine triphosphatase p97, and degradation by the proteasome. Processing-defective mutants of Hh are degraded by the same ERAD components. Thus, processing of the Hh precursor competes with its rapid degradation, explaining the impaired Hh signaling of processing-defective mutants, such as those causing human holoprosencephaly.<\/jats:p>","DOI":"10.1083\/jcb.201008090","type":"journal-article","created":{"date-parts":[[2011,3,2]],"date-time":"2011-03-02T16:32:12Z","timestamp":1299083532000},"page":"825-838","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":130,"title":["Processing and turnover of the Hedgehog protein in the endoplasmic reticulum"],"prefix":"10.1083","volume":"192","author":[{"given":"Xin","family":"Chen","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"},{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"},{"name":"Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 115, Republic of China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Tukachinsky","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 115, Republic of China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Jao","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Ru","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 115, Republic of China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Yun","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 115, Republic of China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Mueller","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Schulman","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom A.","family":"Rapoport","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Salic","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 1 , 2 ; and 3"},{"name":"Department of Cell Biology 1 , 2 ; and 3"},{"name":"Department of Molecular Biology, Massachusetts General Hospital; Harvard Medical School, Boston, MA 02115 1 , 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2011,2,28]]},"reference":[{"key":"2023072905155287000_bib1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/35050524","article-title":"Hrd1p\/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation","volume":"3","author":"Bays","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"2023072905155287000_bib2","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1091\/mbc.12.12.4114","article-title":"HRD4\/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins","volume":"12","author":"Bays","year":"2001","journal-title":"Mol. Biol. Cell."},{"key":"2023072905155287000_bib3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1083\/jcb.200910042","article-title":"Stringent requirement for HRD1, SEL1L, and OS-9\/XTP3-B for disposal of ERAD-LS substrates","volume":"188","author":"Bernasconi","year":"2010","journal-title":"J. Cell Biol."},{"key":"2023072905155287000_bib4","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1432-1033.1974.tb03599.x","article-title":"A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels","volume":"46","author":"Bonner","year":"1974","journal-title":"Eur. J. Biochem."},{"key":"2023072905155287000_bib5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1091\/mbc.9.1.209","article-title":"Der3p\/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins","volume":"9","author":"Bordallo","year":"1998","journal-title":"Mol. Biol. Cell."},{"key":"2023072905155287000_bib6","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/S0021-9258(19)69848-0","article-title":"Phase separation of integral membrane proteins in Triton X-114 solution","volume":"256","author":"Bordier","year":"1981","journal-title":"J. Biol. Chem."},{"key":"2023072905155287000_bib7","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1128\/MCB.15.4.2294","article-title":"Proteolytic processing yields two secreted forms of sonic hedgehog","volume":"15","author":"Bumcrot","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"2023072905155287000_bib8","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.cell.2006.05.043","article-title":"Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins","volume":"126","author":"Carvalho","year":"2006","journal-title":"Cell."},{"key":"2023072905155287000_bib9","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1126\/science.1064437","article-title":"Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal","volume":"293","author":"Chamoun","year":"2001","journal-title":"Science."},{"key":"2023072905155287000_bib10","first-page":"634","article-title":"Sterols accelerate degradation of hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase encoded by a constitutively expressed cDNA","volume":"5","author":"Chin","year":"1985","journal-title":"Mol. Cell. Biol."},{"key":"2023072905155287000_bib11","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/ncb1689","article-title":"OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD","volume":"10","author":"Christianson","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"2023072905155287000_bib12","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.cell.2006.05.045","article-title":"A luminal surveillance complex that selects misfolded glycoproteins for ER-associated degradation","volume":"126","author":"Denic","year":"2006","journal-title":"Cell."},{"key":"2023072905155287000_bib13","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1096\/fasebj.5.15.1743438","article-title":"Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing","volume":"5","author":"Elbein","year":"1991","journal-title":"FASEB J."},{"key":"2023072905155287000_bib14","doi-asserted-by":"publisher","first-page":"14422","DOI":"10.1073\/pnas.251401598","article-title":"The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum","volume":"98","author":"Fang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905155287000_bib15","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1083\/jcb.151.1.69","article-title":"Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p","volume":"151","author":"Gardner","year":"2000","journal-title":"J. Cell Biol."},{"key":"2023072905155287000_bib16","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/ncb1445","article-title":"A complex of Yos9p and the HRD ligase integrates endoplasmic reticulum quality control into the degradation machinery","volume":"8","author":"Gauss","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"2023072905155287000_bib17","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/0092-8674(85)90078-9","article-title":"Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme","volume":"41","author":"Gil","year":"1985","journal-title":"Cell."},{"key":"2023072905155287000_bib18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0092-8674(01)80011-8","article-title":"Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins","volume":"91","author":"Hall","year":"1997","journal-title":"Cell."},{"key":"2023072905155287000_bib19","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1083\/jcb.125.2.299","article-title":"Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast","volume":"125","author":"Hampton","year":"1994","journal-title":"J. Cell Biol."},{"key":"2023072905155287000_bib20","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1042\/BJ20041241","article-title":"TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum","volume":"388","author":"Hassink","year":"2005","journal-title":"Biochem. J."},{"key":"2023072905155287000_bib21","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1093\/emboj\/cdg107","article-title":"A role for N-glycanase in the cytosolic turnover of glycoproteins","volume":"22","author":"Hirsch","year":"2003","journal-title":"EMBO J."},{"key":"2023072905155287000_bib22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nature07962","article-title":"The ubiquitylation machinery of the endoplasmic reticulum","volume":"458","author":"Hirsch","year":"2009","journal-title":"Nature."},{"key":"2023072905155287000_bib23","doi-asserted-by":"publisher","first-page":"20914","DOI":"10.1074\/jbc.M709336200","article-title":"Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP","volume":"283","author":"Hosokawa","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2023072905155287000_bib24","doi-asserted-by":"publisher","first-page":"17061","DOI":"10.1074\/jbc.M809725200","article-title":"Human OS-9, a lectin required for glycoprotein endoplasmic reticulum-associated degradation, recognizes mannose-trimmed N-glycans","volume":"284","author":"Hosokawa","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2023072905155287000_bib25","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/ncb746","article-title":"Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48","volume":"4","author":"Jarosch","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"2023072905155287000_bib26","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1042\/BST20051509","article-title":"The mechanism of hedgehog signal transduction","volume":"33","author":"Kalderon","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"2023072905155287000_bib27","doi-asserted-by":"publisher","first-page":"32846","DOI":"10.1074\/jbc.M002063200","article-title":"Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress","volume":"275","author":"Kokame","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2023072905155287000_bib28","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1242\/dev.121.8.2349","article-title":"Patterning of the neural ectoderm of Xenopus laevis by the amino-terminal product of hedgehog autoproteolytic cleavage","volume":"121","author":"Lai","year":"1995","journal-title":"Development."},{"key":"2023072905155287000_bib29","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1126\/science.7985023","article-title":"Autoproteolysis in hedgehog protein biogenesis","volume":"266","author":"Lee","year":"1994","journal-title":"Science."},{"key":"2023072905155287000_bib30","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nature02592","article-title":"A membrane protein required for dislocation of misfolded proteins from the ER","volume":"429","author":"Lilley","year":"2004","journal-title":"Nature."},{"key":"2023072905155287000_bib31","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1126\/science.1098020","article-title":"The Hedgehog response network: sensors, switches, and routers","volume":"304","author":"Lum","year":"2004","journal-title":"Science."},{"key":"2023072905155287000_bib32","doi-asserted-by":"publisher","first-page":"17026","DOI":"10.1073\/pnas.0507848102","article-title":"Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly","volume":"102","author":"Maity","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905155287000_bib33","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/384176a0","article-title":"Biochemical evidence that patched is the Hedgehog receptor","volume":"384","author":"Marigo","year":"1996","journal-title":"Nature."},{"key":"2023072905155287000_bib34","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1083\/jcb.200605196","article-title":"SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER","volume":"175","author":"Mueller","year":"2006","journal-title":"J. Cell Biol."},{"key":"2023072905155287000_bib35","doi-asserted-by":"publisher","first-page":"12325","DOI":"10.1073\/pnas.0805371105","article-title":"SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins","volume":"105","author":"Mueller","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905155287000_bib36","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.bcp.2004.01.002","article-title":"Regulation of Hedgehog signaling: a complex story","volume":"67","author":"Ogden","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"2023072905155287000_bib37","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/374363a0","article-title":"The product of hedgehog autoproteolytic cleavage active in local and long-range signalling","volume":"374","author":"Porter","year":"1995","journal-title":"Nature."},{"key":"2023072905155287000_bib38","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0092-8674(00)80074-4","article-title":"Hedgehog patterning activity: role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain","volume":"86","author":"Porter","year":"1996","journal-title":"Cell."},{"key":"2023072905155287000_bib39","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1126\/science.274.5285.255","article-title":"Cholesterol modification of hedgehog signaling proteins in animal development","volume":"274","author":"Porter","year":"1996","journal-title":"Science."},{"key":"2023072905155287000_bib40","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1128\/MCB.22.2.626-634.2002","article-title":"AAA-ATPase p97\/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation","volume":"22","author":"Rabinovich","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2023072905155287000_bib41","doi-asserted-by":"publisher","first-page":"E921","DOI":"10.1002\/humu.21090","article-title":"The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis","volume":"30","author":"Roessler","year":"2009","journal-title":"Hum. Mutat."},{"key":"2023072905155287000_bib42","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1101\/gad.8.11.1311","article-title":"Xenopus embryos regulate the nuclear localization of XMyoD","volume":"8","author":"Rupp","year":"1994","journal-title":"Genes Dev."},{"key":"2023072905155287000_bib43","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/S1097-2765(00)80446-3","article-title":"Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts","volume":"5","author":"Salic","year":"2000","journal-title":"Mol. Cell."},{"key":"2023072905155287000_bib44","doi-asserted-by":"publisher","first-page":"15027","DOI":"10.1073\/pnas.1009972107","article-title":"Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners","volume":"107","author":"Schulman","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072905155287000_bib45","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.jmb.2005.10.020","article-title":"The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway","volume":"354","author":"Schulze","year":"2005","journal-title":"J. Mol. Biol."},{"key":"2023072905155287000_bib46","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1083\/jcb.200906110","article-title":"The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER","volume":"186","author":"Stagg","year":"2009","journal-title":"J. Cell Biol."},{"key":"2023072905155287000_bib47","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/384129a0","article-title":"The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog","volume":"384","author":"Stone","year":"1996","journal-title":"Nature."},{"key":"2023072905155287000_bib48","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.1101\/gad.933301","article-title":"A conserved ubiquitin ligase of the nuclear envelope\/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation","volume":"15","author":"Swanson","year":"2001","journal-title":"Genes Dev."},{"key":"2023072905155287000_bib49","doi-asserted-by":"publisher","first-page":"42889","DOI":"10.1074\/jbc.M405161200","article-title":"Functional characterization of sonic hedgehog mutations associated with holoprosencephaly","volume":"279","author":"Traiffort","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023072905155287000_bib50","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1083\/jcb.200207120","article-title":"Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1","volume":"159","author":"Tsai","year":"2002","journal-title":"J. Cell Biol."},{"key":"2023072905155287000_bib51","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/S0092-8674(01)00289-6","article-title":"Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin","volume":"104","author":"Tsai","year":"2001","journal-title":"Cell."},{"key":"2023072905155287000_bib52","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science.1159293","article-title":"ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER","volume":"321","author":"Ushioda","year":"2008","journal-title":"Science."},{"key":"2023072905155287000_bib53","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1093\/emboj\/20.12.3124","article-title":"Sec61p-independent degradation of the tail-anchored ER membrane protein Ubc6p","volume":"20","author":"Walter","year":"2001","journal-title":"EMBO J."},{"key":"2023072905155287000_bib54","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/S0092-8674(00)81054-5","article-title":"The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol","volume":"84","author":"Wiertz","year":"1996","journal-title":"Cell."},{"key":"2023072905155287000_bib55","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.semcdb.2010.02.007","article-title":"ERAD substrate recognition in budding yeast","volume":"21","author":"Xie","year":"2010","journal-title":"Semin. Cell Dev. Biol."},{"key":"2023072905155287000_bib56","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/414652a","article-title":"The AAA ATPase Cdc48\/p97 and its partners transport proteins from the ER into the cytosol","volume":"414","author":"Ye","year":"2001","journal-title":"Nature."},{"key":"2023072905155287000_bib57","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1038\/nature02656","article-title":"A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol","volume":"429","author":"Ye","year":"2004","journal-title":"Nature."}],"container-title":["Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/192\/5\/825\/1868954\/jcb_201008090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/192\/5\/825\/1868954\/jcb_201008090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T05:16:21Z","timestamp":1690607781000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/192\/5\/825\/36380\/Processing-and-turnover-of-the-Hedgehog-protein-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,28]]},"references-count":57,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,3,7]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.201008090","relation":{},"ISSN":["1540-8140","0021-9525"],"issn-type":[{"value":"1540-8140","type":"electronic"},{"value":"0021-9525","type":"print"}],"subject":[],"published":{"date-parts":[[2011,2,28]]}}}