Proteasome pathway operates for the degradation of ornithine decarboxylase in intact cells.
Ornithine decarboxylase (ODC) is degraded in an ATP-dependent manner in vitro by the 26 S proteasome in the presence of antizyme, an ODC destabilizing protein induced by polyamines. In the present study we examined whether the proteasome catalyses ODC degradation in living mammalian cells. Lactacystin, the most selective proteasome inhibitor, strongly inhibited the degradation of ODC that had been induced in hepatoma tissue-culture (HTC) cells by refeeding with fresh medium. Furthermore the inhibitor inhibited the rapid degradation of ODC that had been induced by hypotonic shock. Interestingly, hypertonic shock was found to increase the proportion of OD present as a complex with antizyme (the ratio of ODC-antizyme complex to total ODC). Cycloheximide, which partly inhibited rapid ODC degradation caused by hypertonic shock, also part inhibited the increase in the ratio of ODC-antizyme complex total ODC. These results suggest that a common ODC degradation pathway, namely the antizyme-dependent and 26 proteasome-catalysed ODC degradation pathway, is also operating in intact cells for osmoregulated ODC degradation.
Murakami
Y
Y
Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
Tanahashi
N
N
Tanaka
K
K
Omura
S
S
Hayashi
S
S
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D009997:Osmotic Pressure; D046988:Proteasome Endopeptidase Complex; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D065108:Ornithine Decarboxylase Inhibitors; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D009955:Ornithine Decarboxylase; D000111:Acetylcysteine