ER protein quality control and proteasome-mediated protein degradation

A variety of mutant polypeptides that are associated with human disease are treated for degradation by an endoplasmic reticulum (ER) quality control s ystem. In addition, physiological signals and viral gene products can targe t the degradation of several ER resident proteins and secreted proteins pas sing through the ER. Although the mechanism of protein quality control and the site of degradation were obscure, recent data indicate that degradation requires the cytosolic proteasome. Biochemical and genetic analyses have i ndicated that both lumenal and integral membrane proteins are selected for proteolysis and exported to the cytosol by a process that in several cases requires associated molecular chaperones.