Discrimination between ubiquitin-dependent and ubiquitin-independent proteolytic pathways by the 26S proteasome subunit 5a.
The 26S proteasome subunit 5a binds polyubiquitin chains and has previously been shown to inhibit the degradation of mitotic cyclins. Presumably inhibition results from S5a binding and preventing recognition of Ub-cyclin conjugates by the 26S proteasome. Here we show that S5a does not inhibit the degradation of full-length ornithine decarboxylase (ODC) consistent with previous reports that the enzyme is degraded in an antizyme-dependent, but ubiquitin-independent reaction. S5a does, however, inhibit degradation of short ODC translation products generated by internal initiation events. Because in vitro translation often produces some shortened products, the existence of ubiquitin conjugated to a 35S-labeled protein is not necessarily evidence that the full-length protein is a substrate of the Ub-dependent proteolytic pathway.
Mahaffey
D
D
Department of Biochemistry, University of Utah, School of Medicine, Salt Lake City 84132, USA.
Rechsteiner
M
M
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009113:Muramidase / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014452:Ubiquitins; C067713:lactacystin; D009113:Muramidase; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D009955:Ornithine Decarboxylase; D000111:Acetylcysteine