A PROTEIN TRANSLOCATION DEFECT LINKED TO UBIQUITIN CONJUGATION AT THE ENDOPLASMIC-RETICULUM

UBIQUITIN-Conjugating enzymes function in selective proteolysis pathways and catalyse the covalent attachment of ubiquitin to proteolytic substrates1-4. Here we report the identification of an integral membrane ubiquitin-conjugating enzyme. This enzyme, UBC6, localizes to the endoplasmic reticulum (ER), with the catalytic domain facing the cytosol. ubc6 loss-of-function mutants suppress the protein translocation defect caused by a mutation in SEC61, which encodes a key component of a multisubunit protein translocation apparatus of the ER5-11. The expression of the sec61 mutant phenotype requires both the activity of UBC6 and its localization at the ER membrane. This suggests that UBC6 may mediate selective degradation of ER membrane proteins and that the protein translocation defect of sec61 may be caused by proteolysis of components of a structurally distorted mutant translocation apparatus.