Role of Cue1p in ubiquitination and degradation at the ER surface.
Endoplasmic reticulum (ER) degradation of aberrant proteins is mediated by the ubiquitin-proteasome pathway. Here, a membrane-bound component of the ubiquitin system, Cue1p, was identified. It was shown to recruit the soluble ubiquitin-conjugating enzyme Ubc7p to the ER membrane. In the absence of Cue1p, unassembled and thus cytosolically mislocalized Ubc7p was unable to participate in ER degradation or in the turnover of soluble non-ER proteins. Moreover, ubiquitination by Cue1p-assembled Ubc7p and Ubc6p was a prerequisite for retrograde transport of lumenal substrates out of the ER, which suggests that ubiquitination is mechanistically integrated into the ER degradation process.
Biederer
T
T
Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13122 Berlin, Germany.
Volkwein
C
C
Sommer
T
T
D000595:Amino Acid Sequence; D001692:Biological Transport; D002268:Carboxypeptidases / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043402:Cathepsin A; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008025:Ligases / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D000069816:SEC Translocation Channels; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism
C109280:CUE1 protein, S cerevisiae; D002352:Carrier Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D000069816:SEC Translocation Channels; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C082461:UBC6 protein, S cerevisiae; C489967:UBE2J1 protein, human; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D002268:Carboxypeptidases; D043402:Cathepsin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases