Cue1p is an N-terminally anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). Cue1p contains a CUE domain, which for several proteins is known to bind ubiquitin. We now establish that the CUE domain is dispensable for ERAD of substrates of both Hrd1p and Doa10p and that the Cue1p transmembrane domain is similarly not required for degradation of the Hrd1p substrate CPY. Cue1p interacts with the ERAD E2 Ubc7p in vivo. We show that a discrete C-terminal Ubc7p binding region (U7BR) of Cue1p is required for ERAD and for Ubc7p-dependent ubiquitylation by Hrd1p in vitro. Strikingly, when Ubc7p is stabilized by direct anchoring to the ER membrane, the U7BR is sufficient to restore ERAD in cells lacking Cue1p. Thus, discrete E2 binding sites independent of ubiquitin ligase domains have the potential to activate ubiquitylation.
We have not found any resources mentioned in this publication.
SciCrunch is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to SciCrunch, however this is not currently a free service.