DER1, A NOVEL PROTEIN SPECIFICALLY REQUIRED FOR ENDOPLASMIC-RETICULUMDEGRADATION IN YEAST

The endoplasmic reticulum (ER) of the yeast Saccharomyces cerevisiae c ontains a proteolytic system able to selectively degrade misfolded lum enal secretory proteins. For examination of the components involved in this degradation process, mutants were isolated. They could be divide d into four complementation groups, The mutations led to stabilization of two different substrates for this process. The mutant classes were called 'der' for 'degradation in the ER'. DER1 was cloned by compleme ntation of the der1-2 mutation. The DER1 gene codes for a novel, hydro phobic protein, that is localized to the ER. Deletion of DER1 abolishe d degradation of the substrate proteins. The function of the Der1 prot ein seems to be specifically required for the degradation process asso ciated with the ER. The depletion of Der1 from cells causes neither de tectable growth phenotypes nor a general accumulation of unfolded prot eins in the ER. In DER1-deleted cells, a substrate protein for ER degr adation is retained in the ER by the same mechanism which also retains lumenal ER residents. This suggests that DER1 acts in a process that directly removes protein from the folding environment of the ER.