title: Degradation of ornithine decarboxylase in mammalian cells is ATP dependent but ubiquitin independent.
abstract: Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines in mammalian cells is characterized by an extremely short half-life. In the present study, ODC degradation was investigated in 653-1 mouse myeloma cells that overproduce ODC and in ts85 cells that are thermosensitive for conjunction of ubiquitin to target proteins. Addition of 2-deoxyglucose and dinitrophenol (agents that efficiently deplete cellular ATP) to the growth medium of these cells inhibited ODC degradation. In contrast, chloroquine and leupeptin, inhibitors of intralysosomal proteolysis, did not affect ODC degradation. Shifting ts85 cells to 42 degrees C (a non-permissive temperature that inhibited conjugation of ubiquitin to target proteins) did not prevent ODC degradation. The ATP-dependent degradation of ODC in 653-1 cells was inhibited substantially by N alpha-tosyl-L-lysine chloromethane (TosPheMeCl), iodoacetamide and o-phenanthroline. These results suggest that ODC degradation occurs via a non-lysosomal. ATP-requiring and ubiquitin-independent cellular proteolytic mechanism, and that serine proteases and enzymes containing sulphydryl groups and metalloenzyme(s) may be involved in this process.
authors.affiliation: Department of Virology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Rosenberg-Hasson
authors.forename: Z
authors.initials: Z
authors.lastname: Bercovich
authors.forename: A
authors.initials: A
authors.lastname: Ciechanover
authors.forename: C
authors.initials: C
authors.lastname: Kahana
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D008322:Mammals / Q000502:physiology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000502:physiology*
chemical_list: D011073:Polyamines; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D009955:Ornithine Decarboxylase