ER Protein Folding and Degradation

In eukaryotes, approximately 30% of all newly synthesized proteins pass through the endoplasmic reticulum (ER), where they undergo folding and maturation. A significant fraction of nascent proteins may fail to fold properly, which if not cleared efficiently may contribute to disease pathogenesis. These misfolded proteins in the ER are disposed of by a quality-control process known as ER-associated degradation (ERAD). ERAD is the first line of defense to recruit and retrotranslocate misfolded ER proteins for cytosolic proteasomal degradation. ERAD helps maintain a favorable folding environment for wildtype ER proteins, and has been implicated in over 70 human diseases. The long-term goal of our research program is to gain a comprehensive understanding of the cellular and physiological functions of mammalian ERAD.