{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:19:24Z","timestamp":1779351564886,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2000,12,4]],"date-time":"2000-12-04T00:00:00Z","timestamp":975888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Cell Biol"],"published-print":{"date-parts":[[2001,1]]},"DOI":"10.1038\/35050524","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T08:46:14Z","timestamp":1027673174000},"page":"24-29","source":"Crossref","is-referenced-by-count":399,"title":["Hrd1p\/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation"],"prefix":"10.1038","volume":"3","author":[{"given":"Nathan W.","family":"Bays","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard G.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda P.","family":"Seelig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio A.","family":"Joazeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randolph Y.","family":"Hampton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2000,12,4]]},"reference":[{"key":"BFncb0101_24_CR1","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1006\/scdb.1999.0321","volume":"10","author":"JL Brodsky","year":"1999","unstructured":"Brodsky, J. L. & McCracken, A. A. ER protein quality control and proteasome-mediated protein degradation. Semin. Cell Dev. Biol. 10, 507\u2013513 ( 1999).","journal-title":"Semin. Cell Dev. Biol."},{"key":"BFncb0101_24_CR2","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev.genet.30.1.405","volume":"30","author":"M Hochstrasser","year":"1996","unstructured":"Hochstrasser, M. Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 30, 405\u2013439 (1996).","journal-title":"Annu. Rev. Genet."},{"key":"BFncb0101_24_CR3","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1091\/mbc.7.12.2029","volume":"7","author":"RY Hampton","year":"1996","unstructured":"Hampton, R. Y., Gardner, R. G. & Rine, J. Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol. Biol. Cell 7, 2029\u20132044 (1996).","journal-title":"Mol. Biol. Cell"},{"key":"BFncb0101_24_CR4","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1091\/mbc.11.5.1697","volume":"11","author":"SK Wilhovsky","year":"2000","unstructured":"Wilhovsky, S. K., Gardner, R. G. & Hampton, R. Y. HRD gene dependence of ER-associated degradation. Mol. Biol. Cell 11, 1697\u2013 1708 (2000).","journal-title":"Mol. Biol. Cell"},{"key":"BFncb0101_24_CR5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/35017001","volume":"2","author":"R Friedlander","year":"2000","unstructured":"Friedlander, R., Jarosch, E., Urban, J., Volkwein, C. & Sommer, T. A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nature Cell Biol. 2, 379\u2013384 (2000).","journal-title":"Nature Cell Biol."},{"key":"BFncb0101_24_CR6","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/S0092-8674(00)80835-1","volume":"101","author":"KJ Travers","year":"2000","unstructured":"Travers, K. J. et al. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101, 249\u2013258 ( 2000).","journal-title":"Cell"},{"key":"BFncb0101_24_CR7","doi-asserted-by":"publisher","first-page":"11364","DOI":"10.1073\/pnas.96.20.11364","volume":"96","author":"KL Lorick","year":"1999","unstructured":"Lorick, K. L. et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl Acad. Sci. USA 96, 11364\u201311369 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb0101_24_CR8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1126\/science.286.5438.309","volume":"286","author":"CA Joazeiro","year":"1999","unstructured":"Joazeiro, C. A. et al. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science 286, 309\u2013312 (1999).","journal-title":"Science"},{"key":"BFncb0101_24_CR9","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S1097-2765(00)80482-7","volume":"3","author":"T Ohta","year":"1999","unstructured":"Ohta, T., Michel, J. J., Schottelius, A. J. & Xiong, Y. ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol. Cell 3, 535\u2013541 (1999).","journal-title":"Mol. Cell"},{"key":"BFncb0101_24_CR10","doi-asserted-by":"crossref","first-page":"8929","DOI":"10.1016\/S0021-9258(18)68397-8","volume":"263","author":"M Nakanishi","year":"1988","unstructured":"Nakanishi, M., Goldstein, J. L. & Brown, M. S. Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme. J. Biol. Chem. 263, 8929\u20138937 (1988).","journal-title":"J. Biol. Chem."},{"key":"BFncb0101_24_CR11","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1083\/jcb.125.2.299","volume":"125","author":"RY Hampton","year":"1994","unstructured":"Hampton, R. Y. & Rine, J. Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J. Cell Biol. 125, 299\u2013 312 (1994).","journal-title":"J. Cell Biol."},{"key":"BFncb0101_24_CR12","doi-asserted-by":"publisher","first-page":"12944","DOI":"10.1073\/pnas.94.24.12944","volume":"94","author":"RY Hampton","year":"1997","unstructured":"Hampton, R. Y. & Bhakta, H. Ubiquitin-mediated regulation of 3-hydroxy-3-methylglutaryl-CoA reductase. Proc. Natl Acad. Sci. USA 94, 12944\u201312948 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb0101_24_CR13","doi-asserted-by":"publisher","first-page":"31671","DOI":"10.1074\/jbc.274.44.31671","volume":"274","author":"RG Gardner","year":"1999","unstructured":"Gardner, R. G. & Hampton, R. Y. A highly conserved signal controls degradation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in eukaryotes. J. Biol. Chem. 274, 31671\u201331678 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFncb0101_24_CR14","first-page":"58","volume-title":"Methods in Enzymology","author":"SR Cronin","year":"1999","unstructured":"Cronin, S. R. & Hampton, R. Y. in Methods in Enzymology Vol. 302 (ed. Conn, P. M.) 58\u201373 (Academic Press, San Diego and London, 1999)."},{"key":"BFncb0101_24_CR15","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1091\/mbc.9.1.209","volume":"9","author":"J Bordallo","year":"1998","unstructured":"Bordallo, J., Plemper, R. K., Finger, A. & Wolf, D. H. Der3p\u2013Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol. Biol. Cell 9, 209\u2013222 ( 1998).","journal-title":"Mol. Biol. Cell"},{"key":"BFncb0101_24_CR16","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1126\/science.279.5354.1216","volume":"279","author":"W Zachariae","year":"1998","unstructured":"Zachariae, W. et al. Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins. Science 279, 1216\u20131219 ( 1998).","journal-title":"Science"},{"key":"BFncb0101_24_CR17","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1101\/gad.13.12.1614","volume":"13","author":"JH Seol","year":"1999","unstructured":"Seol, J. H. et al. Cdc53\/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev. 13, 1614\u20131626 (1999).","journal-title":"Genes Dev."},{"key":"BFncb0101_24_CR18","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1126\/science.273.5282.1725","volume":"273","author":"MM Hiller","year":"1996","unstructured":"Hiller, M. M., Finger, A., Schweiger, M. & Wolf, D. H. ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway. Science 273, 1725\u2013 1728 (1996).","journal-title":"Science"},{"key":"BFncb0101_24_CR19","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/365176a0","volume":"365","author":"T Sommer","year":"1993","unstructured":"Sommer, T. & Jentsch, S. A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. Nature 365, 176\u2013179 ( 1993).","journal-title":"Nature"},{"key":"BFncb0101_24_CR20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1083\/jcb.151.1.69","volume":"151","author":"RG Gardner","year":"2000","unstructured":"Gardner, R. G. et al. ER degradation requires lumen to cytosol signaling: transmembrane control of Hrd1p by Hrd3p. J. Cell Biol. 151, 69\u201382 (2000).","journal-title":"J. Cell Biol."},{"key":"BFncb0101_24_CR21","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1073\/pnas.44.2.162","volume":"44","author":"FM Richards","year":"1958","unstructured":"Richards, F. M. On the enzymic activity of subtilisin-modified ribonuclease. Proc. Natl Acad. Sci. USA 44, 162\u2013166 (1958).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb0101_24_CR22","first-page":"317","volume-title":"The Enzymes","author":"P Blackburn","year":"1982","unstructured":"Blackburn, P. & Moore, S. in The Enzymes (ed. Boyer, P. D.) 317\u2013440 (Academic Press, San Diego, 1982)."},{"key":"BFncb0101_24_CR23","doi-asserted-by":"publisher","first-page":"8945","DOI":"10.1074\/jbc.275.12.8945","volume":"275","author":"S Fang","year":"2000","unstructured":"Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H. & Weissman, A. M. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem. 275, 8945\u20138951 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFncb0101_24_CR24","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1074\/jbc.271.1.302","volume":"271","author":"H Gonen","year":"1996","unstructured":"Gonen, H. et al. Isolation, characterization, and partial purification of a novel ubiquitin-protein ligase, E3. Targeting of protein substrates via multiple and distinct recognition signals and conjugating enzymes. J. Biol. Chem. 271, 302\u2013310 ( 1996).","journal-title":"J. Biol. Chem."},{"key":"BFncb0101_24_CR25","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/0006-291X(85)91050-2","volume":"128","author":"A Hershko","year":"1985","unstructured":"Hershko, A. & Heller, H. Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem. Biophys. Res. Commun. 128, 1079\u20131086 ( 1985).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFncb0101_24_CR26","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1126\/science.278.5337.460","volume":"278","author":"R Visintin","year":"1997","unstructured":"Visintin, R., Prinz, S. & Amon, A. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278, 460\u2013463 (1997).","journal-title":"Science"},{"key":"BFncb0101_24_CR27","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1101\/gad.13.13.1678","volume":"13","author":"WM Gray","year":"1999","unstructured":"Gray, W. M. et al. Identification of an SCF ubiquitin-ligase complex required for auxin response in Arabidopsis thaliana. Genes Dev. 13, 1678\u20131691 (1999).","journal-title":"Genes Dev."},{"key":"BFncb0101_24_CR28","doi-asserted-by":"publisher","first-page":"18785","DOI":"10.1074\/jbc.274.26.18785","volume":"274","author":"S Kumar","year":"1999","unstructured":"Kumar, S., Talis, A. L. & Howley, P. M. Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination. J. Biol. Chem. 274 , 18785\u201318792 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFncb0101_24_CR29","doi-asserted-by":"publisher","first-page":"32848","DOI":"10.1074\/jbc.273.49.32848","volume":"273","author":"RK Plemper","year":"1998","unstructured":"Plemper, R. K., Egner, R., Kuchler, K. & Wolf, D. H. Endoplasmic reticulum degradation of a mutated ATP-binding cassette transporter Pdr5 proceeds in a concerted action of Sec61 and the proteasome. J. Biol. Chem. 273, 32848\u201332856 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFncb0101_24_CR30","doi-asserted-by":"publisher","first-page":"4535","DOI":"10.1002\/j.1460-2075.1990.tb07905.x","volume":"9","author":"W Seufert","year":"1990","unstructured":"Seufert, W., McGrath, J. P. & Jentsch, S. UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin-conjugating enzymes involved in protein degradation. EMBO J. 9, 4535\u20134541 ( 1990).","journal-title":"EMBO J."},{"key":"BFncb0101_24_CR31","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/361369a0","volume":"361","author":"J Jungmann","year":"1993","unstructured":"Jungmann, J., Reins, H. A., Schobert, C. & Jentsch, S. Resistance to cadmium mediated by ubiquitin-dependent proteolysis. Nature 361, 369\u2013371 ( 1993).","journal-title":"Nature"},{"key":"BFncb0101_24_CR32","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1126\/science.278.5344.1806","volume":"278","author":"T Biederer","year":"1997","unstructured":"Biederer, T., Volkwein, C. & Sommer, T. Role of Cue1p in ubiquitination and degradation at the ER surface. Science 278, 1806\u2013 1809 (1997).","journal-title":"Science"},{"key":"BFncb0101_24_CR33","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1093\/emboj\/19.4.550","volume":"19","author":"K Hill","year":"2000","unstructured":"Hill, K. & Cooper, A. A. Degradation of unassembled Vph1p reveals novel aspects of the yeast ER quality control system. EMBO J. 19, 550\u2013561 ( 2000).","journal-title":"EMBO J."},{"key":"BFncb0101_24_CR34","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0003-2697(86)90166-1","volume":"156","author":"PS Swerdlow","year":"1986","unstructured":"Swerdlow, P. S., Finley, D. & Varshavsky, A. Enhancement of immunoblot sensitivity by heating of hydrated filters. Anal. Biochem. 156, 147\u2013153 (1986).","journal-title":"Anal. Biochem."},{"key":"BFncb0101_24_CR35","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1046\/j.1365-2443.1998.00227.x","volume":"3","author":"T Anan","year":"1998","unstructured":"Anan, T. et al. Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes . Genes Cells 3, 751\u2013763 (1998).","journal-title":"Genes Cells"},{"key":"BFncb0101_24_CR36","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1177\/25.7.894009","volume":"25","author":"IT Young","year":"1977","unstructured":"Young, I. T. Proof without prejudice: use of the Kolmogorov\u2013Smirnov test for the analysis of histograms from flow systems and other sources. J. Histochem. Cytochem. 25, 935\u2013941 (1977).","journal-title":"J. Histochem. Cytochem."},{"key":"BFncb0101_24_CR37","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/yea.320110408","volume":"11","author":"RD Gietz","year":"1995","unstructured":"Gietz, R. D., Schiestl, R. H., Willems, A. R. & Woods, R. A. Studies on the transformation of intact yeast cells by the LiAc\/SS-DNA\/PEG procedure. Yeast 11, 355\u2013 360 (1995).","journal-title":"Yeast"},{"key":"BFncb0101_24_CR38","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1002\/pro.5560020307","volume":"2","author":"JS Kim","year":"1993","unstructured":"Kim, J. S. & Raines, R. T. Ribonuclease S-peptide as a carrier in fusion proteins. Protein Sci. 2, 348\u2013356 (1993).","journal-title":"Protein Sci."}],"container-title":["Nature Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ncb0101_24","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb0101_24.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb0101_24.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T19:58:33Z","timestamp":1684439913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncb0101_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12,4]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001,1]]}},"alternative-id":["BFncb0101_24"],"URL":"https:\/\/doi.org\/10.1038\/35050524","relation":{},"ISSN":["1465-7392","1476-4679"],"issn-type":[{"value":"1465-7392","type":"print"},{"value":"1476-4679","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12,4]]}}}