{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:56:30Z","timestamp":1791939390170,"version":"4.3.4"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,2,3]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    In the endoplasmic reticulum (ER), N-glycans on glycoproteins play important roles in dictating the folding status of proteins by a sophisticated N-glycan\u2013dependent protein quality control machinery. In this study we identified the dysregulation of ER-associated degradation (ERAD) in cells that were defective in the cytosolic deglycosylating enzyme, Ngly1. ERAD dysregulation was caused by an unexpected deglycosylating activity of endo-\u03b2-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosaminidase, another cytosolic deglycosylation enzyme, and this action resulted in the intracellular formation of protein aggregates. Our results clearly point to the critical role of N-glycans even in cytosolic events of the ERAD process by controlling the conformation\/solubility of proteins. This study may also provide a potential mechanism for explaining the pathology of a human genetic disorder caused by mutations in the\n                    <jats:italic>NGLY1<\/jats:italic>\n                    gene.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1414593112","type":"journal-article","created":{"date-parts":[[2015,1,21]],"date-time":"2015-01-21T01:19:22Z","timestamp":1421803162000},"page":"1398-1403","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":126,"title":["Endo-\u03b2-\n                    <i>N<\/i>\n                    -acetylglucosaminidase forms\n                    <i>N<\/i>\n                    -GlcNAc protein aggregates during ER-associated degradation in Ngly1-defective cells"],"prefix":"10.1073","volume":"112","author":[{"given":"Chengcheng","family":"Huang","sequence":"first","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"},{"name":"Graduate School of Science and Engineering, Saitama University, Saitama, Saitama 338-8570, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Harada","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hosomi","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Masahara-Negishi","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Seino","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Fujihira","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Funakoshi","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Collaboration Promotion Unit, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoshi","family":"Dohmae","sequence":"additional","affiliation":[{"name":"Collaboration Promotion Unit, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN\u2013Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama 351-0198, Japan;"},{"name":"Graduate School of Science and Engineering, Saitama University, Saitama, Saitama 338-8570, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,1,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.03.018"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.10.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a013193"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.05.075"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvu068"},{"key":"e_1_3_3_6_2","article-title":"Physiological and molecular functions of the cytosolic peptide:N-glycanase","author":"Hirayama H","year":"2014","unstructured":"H Hirayama, A Hosomi, T Suzuki, Physiological and molecular functions of the cytosolic peptide:N-glycanase. Semin Cell Dev Biol, 2014).","journal-title":"Semin Cell Dev Biol"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1938"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32485-7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.5.1039"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507149"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)15004-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.095919"},{"key":"e_1_3_3_13_2","article-title":"Cytoplasmic peptide:N-glycanase cleaves N-glycans on a carboxypeptidase Y mutant during ERAD in Saccharomyces cerevisiae","author":"Hosomi A","year":"2014","unstructured":"A Hosomi, T Suzuki, Cytoplasmic peptide:N-glycanase cleaves N-glycans on a carboxypeptidase Y mutant during ERAD in Saccharomyces cerevisiae. Biochim Biophys Acta, 2014).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600090"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg107"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2004.11.010"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-006-6975-x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152333599"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700805200"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1104\/pp.112.208900"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.89.97"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4052\/tigg.21.219"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00600-4"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100819"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.22"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81054-5"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1896"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.33.20800"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6210"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29873"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.16.9734"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007151200"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwr073"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.082081"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.05.009"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300328110"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-014-1204-3"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900288106"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O112.018366"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.030007"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198461"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2007.03215.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010545"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2091-13-9"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4962-08.2010"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-07-0433"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1414593112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:47:42Z","timestamp":1649807262000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1414593112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,20]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,2,3]]}},"alternative-id":["10.1073\/pnas.1414593112"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1414593112","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,20]]},"assertion":[{"value":"2015-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}