title: The role of multiubiquitination in dislocation and degradation of the alpha subunit of the T cell antigen receptor.
abstract: Unassembled alpha subunits of the T cell receptor (TCRalpha) are degraded by proteasomes following their dislocation from the endoplasmic reticulum membrane. We previously demonstrated that a variant of TCRalpha lacking lysines (KalphaR) is degraded by this pathway with kinetics indistinguishable from those of the wild type protein (Yu, H., Kaung, G., Kobayashi, S., and Kopito, R. R. (1997) J. Biol. Chem. 272, 20800-20804), demonstrating that ubiquitination on lysines is not required for TCRalpha degradation by the proteasome. Here, we show that dislocation and degradation of TCRalpha and KalphaR are suppressed by dominant negative ubiquitin coexpression and by mutations in the ubiquitin activating enzyme, indicating that their degradation requires a functional ubiquitin pathway. A cytoplasmic TCRalpha variant that mimics a dislocated degradation intermediate was degraded 5 times more rapidly than full-length TCRalpha, suggesting that dislocation from the endoplasmic reticulum membrane is the rate-limiting step in TCRalpha degradation. We conclude that ubiquitination is required both for dislocation and for targeting TCRalpha chains to the proteasome.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: R R
authors.initials: RR
authors.lastname: Kopito
mesh_terms: D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D011948:Receptors, Antigen, T-Cell; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex