ERAD substrates: Which way out?
Global folding of polypeptides entering the endoplasmic reticulum ( ER) starts as soon as they emerge from the narrow Sec61 translocon. Attainment of the native structure can take from several minutes to hours, depending on the gene product. Until then, non-native folding intermediates must be protected from molecular chaperones that recognize misfolded determinants and could prematurely interrupt folding programs by re-directing them to disposal pathways. On the other hand, futile folding attempts must actively be stopped to prevent intraluminal accumulation of defective cargo. This review describes recent advances in understanding how terminally misfolded polypeptides are extracted from the folding environment and directed to specific dislocons within the ER membrane for transfer to the cytoplasm for proteasome-mediated degradation. (c) 2009 Elsevier Ltd. All rights reserved.
Keywords: Endoplasmic reticulum ; Protein folding ; Protein quality control ; ER-associated degradation ; Molecular chaperones ; Folding enzymes ; De-mannosylation ; E3 ubiquitin ligases ; Dislocons ; Reticulum-Associated Degradation ; Glc-Glycoprotein Glucosyltransferase ; Ubiquitin Ligase Complex ; Mannosidase-Like Protein ; Endoplasmic-Reticulum ; Quality-Control ; Misfolded Glycoproteins ; Membrane-Protein ; Udp-Glc ; Saccharomyces-Cerevisiae
Record created on 2011-12-16, modified on 2016-08-09