ROLE OF CUE1P IN UBIQUITINATION AND DEGRADATION AT THE ER SURFACE

Endoplasmic reticulum (ER) degradation of aberrant proteins is mediate d by the ubiquitin-proteasome pathway. Here, a membrane-bound componen t of the ubiquitin system, Cue1p, was identified. It was shown to recr uit the soluble ubiquitin-conjugating enzyme Ubc7p to the ER membrane. In the absence of Cue1p, unassembled and thus cytosolically mislocali zed Ubc7p was unable to participate in ER degradation or in the turnov er of soluble non-ER proteins. Moreover, ubiquitination by Cue1p-assem bled Ubc7p and Ubc6p was a prerequisite for retrograde transport of lu menal substrates out of the ER, which suggests that ubiquitination is mechanistically integrated into the ER degradation process.