{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:32:01Z","timestamp":1783042321814,"version":"3.54.6"},"reference-count":48,"publisher":"American Society for Cell Biology (ASCB)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2015,1,15]]},"abstract":"<jats:p> Misfolded proteins of the secretory pathway are extracted from the endoplasmic reticulum (ER), polyubiquitylated by a protein complex termed the Hmg-CoA reductase degradation ligase (HRD-ligase), and degraded by cytosolic 26S proteasomes. This process is termed ER-associated protein degradation (ERAD). We previously showed that the membrane protein Der1, which is a subunit of the HRD-ligase, is involved in the export of aberrant polypeptides from the ER. Unexpectedly, we also uncovered a close spatial proximity of Der1 and the substrate receptor Hrd3 in the ER lumen. We report here on a mutant Hrd3KR that is selectively defective for ERAD of soluble proteins. Hrd3KR displays subtle structural changes that affect its positioning toward Der1. Furthermore, increased quantities of the ER-resident Hsp70-type chaperone Kar2 and the Hsp40-type cochaperone Scj1 bind to Hrd3KR. Of note, deletion of SCJ1 impairs ERAD of model substrates and causes the accumulation of client proteins at Hrd3. Our data imply a function of Scj1 in the removal of malfolded proteins from the receptor Hrd3, which facilitates their delivery to downstream-acting components like Der1. <\/jats:p>","DOI":"10.1091\/mbc.e14-07-1202","type":"journal-article","created":{"date-parts":[[2014,11,27]],"date-time":"2014-11-27T04:22:30Z","timestamp":1417062150000},"page":"185-194","source":"Crossref","is-referenced-by-count":36,"title":["The interplay of Hrd3 and the molecular chaperone system ensures efficient degradation of malfolded secretory proteins"],"prefix":"10.1091","volume":"26","author":[{"given":"Martin","family":"Mehnert","sequence":"first","affiliation":[{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Sommermeyer","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine, 13125 Berlin, 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