Degradation of ornithine decarboxylase by the 26S proteasome

Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis, Tu rnover of ODC is extremely rapid and highly regulated, and is accelerated w hen polyamine levels increase. Polyamine-stimulated ODC degradation is medi ated by association with antizyme (AZ), an ODC inhibitory protein induced b y polyamines, ODC, in association with AZ, is degraded by the 26S proteasom e in an ATP-dependent, but ubiquitin-independent, manner. The 26S proteasom e irreversibly inactivates ODC prior to its degradation. The inactivation, possibly due to unfolding, is coupled to sequestration of ODC within the 26 S proteasome, This process requires AZ and ATP, but not proteolytic activit y of the 26S proteasome. The carboxyl-terminal region of ODC presumably exp osed 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, unfo lding, translocation, and ultimate degradation mediated by the 26S proteaso me. (C) 2000 Academic Press.