Degradation of Ornithine Decarboxylase by the 26S Proteasome

Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. Turnover of ODC is extremely rapid and highly regulated, and is accelerated when polyamine levels increase. Polyamine-stimulated ODC degradation is mediated by association with antizyme (AZ), an ODC inhibitory protein induced b...

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Published in:Biochemical and biophysical research communications 2000-01, Vol.267 (1), p.1-6
Main Authors: Murakami, Yasuko, Matsufuji, Senya, Hayashi, Shin-ichi, Tanahashi, Nobuyuki, Tanaka, Keiji
Format: Article
Language:English
Subjects:
Animals
Enzyme Inhibitors - metabolism
Models, Chemical
Ornithine Decarboxylase - chemistry
Ornithine Decarboxylase - genetics
Ornithine Decarboxylase - metabolism
Peptide Hydrolases - metabolism
Proteasome Endopeptidase Complex
Proteins - metabolism
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Summary:Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. Turnover of ODC is extremely rapid and highly regulated, and is accelerated when polyamine levels increase. Polyamine-stimulated ODC degradation is mediated by association with antizyme (AZ), an ODC inhibitory protein induced by polyamines. ODC, in association with AZ, is degraded by the 26S proteasome in an ATP-dependent, but ubiquitin-independent, manner. The 26S proteasome irreversibly inactivates ODC prior to its degradation. The inactivation, possibly due to unfolding, is coupled to sequestration of ODC within the 26S proteasome. This process requires AZ and ATP, but not proteolytic activity of the 26S proteasome. The carboxyl-terminal region of ODC presumably exposed by interaction with AZ plays a critical role for being trapped by the 26S proteasome. Thus, the degradation pathway of ODC proceeds as a sequence of multiple distinct processes, including recognition, sequestration, unfolding, translocation, and ultimate degradation mediated by the 26S proteasome.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.1706