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.
Hebert
Daniel N
DN
Department of Biochemistry and Molecular Biology, Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003, USA. dhebert@biochem.umass.edu <dhebert@biochem.umass.edu>
Bernasconi
Riccardo
R
Molinari
Maurizio
M
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism
D018832:Molecular Chaperones; D010455:Peptides; D011506:Proteins; D046988:Proteasome Endopeptidase Complex