title: Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination.
abstract: Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is the most rapidly turned over mammalian enzyme. We have shown that its degradation is accelerated by ODC antizyme, an inhibitory protein induced by polyamines. This is a new type of enzyme regulation and may be a model for selective protein degradation. Here we report the identification of the protease responsible for ODC degradation. Using a cell-free degradation system, we demonstrate that immunodepletion of proteasomes from cell extracts causes almost complete loss of ATP- and antizyme-dependent degradation of ODC. In addition, purified 26S proteasome complex, but not the 20S proteasome, catalyses ODC degradation in the absence of ubiquitin. These results strongly suggest that the 26S proteasome, widely viewed as specific for ubiquitin-conjugated proteins, is the main enzyme responsible for ODC degradation. The 26S proteasome may therefore have a second role in ubiquitin-independent proteolysis.
authors.affiliation: Department of Nutrition, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.forename: S
authors.initials: S
authors.lastname: Matsufuji
authors.forename: T
authors.initials: T
authors.lastname: Kameji
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Igarashi
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Ichihara
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D007163:Immunosorbent Techniques; D008099:Liver / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D065108:Ornithine Decarboxylase Inhibitors; D011506:Proteins; D014452:Ubiquitins; C031017:ornithine decarboxylase antizyme; D000255:Adenosine Triphosphate; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D009955:Ornithine Decarboxylase