title: The human ubiquitin conjugating enzyme UBE2J2 (Ubc6) is a substrate for proteasomal degradation.
abstract: 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.
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
authors.forename: Shuet Y
authors.initials: SY
authors.lastname: Lam
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
authors.forename: Claire
authors.initials: C
authors.lastname: Murphy
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Foley
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Ross
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland. Electronic address: j.fleming@ucc.ie.
authors.forename: John V
authors.initials: JV
authors.lastname: Fleming
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D004795:Enzyme Stability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: C471617:UBE2G2 protein, human; C489966:UBE2J2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex; D003545:Cysteine
keywords: ER associated degradation (ERAD); Ube2G2 (Ubc7); Ube2J2 (Ubc6); Ubiquitin conjugating enzyme; Unfolded protein response (UPR)