{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:23:50Z","timestamp":1791501830836,"version":"4.3.4"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Proteins that are destined for release outside the eukaryotic cell, insertion into the plasma membrane, or delivery to intracellular organelles are processed and folded in the endoplasmic reticulum (ER). An imbalance between the level of nascent proteins entering the ER and the organelle's ability to manage that load results in the accumulation of unfolded proteins. Terminally unfolded proteins are disposed of by ER-associated degradation (ERAD), a pathway that transports the aberrant proteins across the ER membrane into the cytosol for proteasomal degradation. The ERAD pathway was targeted in the mold pathogen\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            by deleting the\n            <jats:italic>hrdA<\/jats:italic>\n            gene, encoding the\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            ortholog of Hrd1, the E3 ubiquitin ligase previously shown to contribute to ERAD in other species. Loss of HrdA was associated with impaired degradation of a folding-defective ERAD substrate, CPY*, as well as activation of the unfolded-protein response (UPR). The \u0394\n            <jats:italic>hrdA<\/jats:italic>\n            mutant showed resistance to voriconazole and reduced thermotolerance but was otherwise unaffected by a variety of environmental stressors. A double-deletion mutant deficient in both HrdA and another component of the same ERAD complex, DerA, was defective in secretion and showed hypersensitivity to ER, thermal, and cell wall stress. However, the \u0394\n            <jats:italic>hrdA<\/jats:italic>\n            \u0394\n            <jats:italic>derA<\/jats:italic>\n            mutant remained virulent in mouse and insect infection models. These data demonstrate that HrdA and DerA support complementary ERAD functions that promote survival under conditions of ER stress but are dispensable for virulence in the host environment.\n          <\/jats:p>","DOI":"10.1128\/ec.00319-12","type":"journal-article","created":{"date-parts":[[2013,1,26]],"date-time":"2013-01-26T04:03:52Z","timestamp":1359173032000},"page":"512-519","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Effects of a Defective Endoplasmic Reticulum-Associated Degradation Pathway on the Stress Response, Virulence, and Antifungal Drug Susceptibility of the Mold Pathogen Aspergillus fumigatus"],"prefix":"10.1128","volume":"12","author":[{"given":"Karthik","family":"Krishnan","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret V.","family":"Powers-Fletcher","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Bick","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl L.","family":"Richie","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Woollett","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Askew","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0808853"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e328335a755"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.28"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2012.08.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02929.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002330"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.2.1.13345"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04341"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04300"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvp166"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35008096"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209235"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.231"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.10.015"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.043"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028865"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000258"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002177"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07522.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0926-6593(66)80120-0"},{"key":"e_1_3_3_22_2","first-page":"9","article-title":"Split-marker recombination for efficient targeted deletion of fungal genes","volume":"50","author":"Catlett N","year":"2002","unstructured":"CatlettN LeeB YoderO TurgeonB. 2002. 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