Bernasconi, Riccardo Galli, Carmela Calanca, Verena Nakajima, Toshihiro Molinari, Maurizio 2010 Sophisticated quality control mechanisms prolong retention of protein-folding intermediates in the endoplasmic reticulum (ER) until maturation while sorting out terminally misfolded polypeptides for ER-associated degradation (ERAD). The presence of structural lesions in the luminal, transmembrane, or cytosolic domains determines the classification of misfolded polypeptides as ERAD-L, -M, or -C substrates and results in selection of distinct degradation pathways. In this study, we show that disposal of soluble (nontransmembrane) polypeptides with luminal lesions (ERAD-LS substrates) is strictly dependent on the E3 ubiquitin ligase HRD1, the associated cargo receptor SEL1L, and two interchangeable ERAD lectins, OS-9 and XTP3-B. These ERAD factors become dispensable for degradation of the same polypeptides when membrane tethered (ERAD-LM substrates). Our data reveal that, in contrast to budding yeast, tethering of mammalian ERAD-L substrates to the membrane changes selection of the degradation pathway. application/pdf https://localhost:5000/ark:/12658/srd1318922 https://susi.usi.ch/global/documents/318922 https://susi.usi.ch/documents/318922/files/bernasconi_jcb_2010.pdf eng info:eu-repo/semantics/altIdentifier/ark/12658/srd1318922 info:eu-repo/semantics/openAccess CC BY-NC-SA The journal of cell biology. - 2010, vol. 188, no. 2, p. 223–235 info:eu-repo/classification/udc/61 Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-LS substrates http://purl.org/coar/resource_type/c_6501