Evolving questions and paradigm shifts in endoplasmic-reticulum-associated degradation (ERAD).
ER-associated degradation (ERAD) is a component of the protein quality control system, ensuring that aberrant polypeptides cannot transit through the secretory pathway. This is accomplished by a complex sequence of events in which unwanted proteins are selected in the ER and exported to the cytosol for degradation by the proteasome. Given that protein quality control can be essential for cell survival, it is not surprising that ERAD is linked to numerous disease states. Here we review the molecular mechanisms of ERAD, its role in metabolic regulation and biomedical implications, and the unanswered questions regarding this process.
McCracken
Ardythe A
AA
Biology Department, University of Nevada, Reno, Nevada 89557, USA. mccracke@unr.edu
Brodsky
Jeffrey L
JL
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D021381:Protein Transport
D005656:Fungal Proteins; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex