ER DEGRADATION OF A MISFOLDED LUMINAL PROTEIN BY THE CYTOSOLIC UBIQUITIN-PROTEASOME PATHWAY

Secretion of proteins is initiated by their uptake into the endoplasmi c reticulum (ER), which possesses a proteolytic system able to degrade misfolded and nonassembled proteins. The ER degradation system was st udied with yeast mutants defective in the breakdown of a mutated solub le vacuolar protein, carboxypeptidase yscY (CPYstar). The ubiquitin-co njugating enzyme Ubc7p participated in the degradation process, which was mediated by tile cytosolic 26S proteasome. It is likely that CPYst ar entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it wa s conjugated with ubiquitin and degraded.