Endoplasmic Reticulum-Associated Degradation and Protein Quality Control

Abstract

Approximately one-third of all polypeptides synthesized in eukaryotes are targeted to the endoplasmic reticulum (ER), and once associated with this compartment they are chemically modified. The folding status of the resulting nascent proteins is then surveyed by molecular chaperones and lectins. To clear the ER of dead-end products, proteins that fail quality control are routed to the cytosol and degraded via ER associated degradation (ERAD). Although many ERAD-requiring factors have been identified and a basic understanding of this pathway has been achieved, numerous questions remain on the mechanisms that lead to the selection and delivery of ERAD substrates.