title: Endoplasmic reticulum-associated degradation.
abstract: Secretory and transmembrane proteins enter the secretory pathway through the protein-conducting Sec61 channel in the membrane of the endoplasmic reticulum. In the endoplasmic reticulum, proteins fold, are frequently covalently modified, and oligomerize before they are packaged into transport vesicles that shuttle them to the Golgi complex. Proteins that misfold in the endoplasmic reticulum are selectively transported back across the endoplasmic reticulum membrane to the cytosol for degradation by proteasomes. Depending on the topology of the defect in the protein, cytosolic or lumenal chaperones are involved in its targeting to degradation. The export channel for misfolded proteins is likely also formed by Sec61p. Export may be powered by AAA-ATPases of the proteasome 19S regulatory particle or Cdc48p/p97. Exported proteins are frequently ubiquitylated prior to degradation and are escorted to the proteasome by polyubiquitin-binding proteins.
authors.affiliation: University of Cambridge, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom. kbr20@cam.ac.uk
authors.forename: Karin
authors.initials: K
authors.lastname: Römisch
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex