The human ubiquitin conjugating enzyme UBE2J2 (Ubc6) is a substrate for proteasomal degradation

• The Ube2J2 protein that mediates ubiquitination of proteins at the ER is unstable.
• Endogenously or ectopically expressed Ube2J2 is targeted for proteasomal degradation.
• Proteasomal degradation of Ube 2J2 is dependent on its ER localization.
• Ube2J2 degradation is dependent on the catalytic activity of the enzyme itself.
• UPR signaling does not increase Ube2J2 steady state expression.

The human Ube2J2 enzyme functions in the ubiquitination of proteins at the ER. Here we demonstrate that it, and a second ubiquitin conjugating (Ubc) enzyme Ube2G2, are unstable, and incubation of transfected cells with proteasome inhibitors increased steady-state protein levels. For Ube2J2, pharmacological induction of the unfolded protein response (UPR) did not significantly alter ectopic protein levels, however the effect of proteasomal inhibition was abolished if the enzyme was inactivated or truncated to disrupt its ER-localization. These results suggest for the first time that the steady state expression of Ubcs’ may be important in regulating the degradation of ER proteins in mammalian cells.