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Antizyme is a polyamine-induced cellular protein that binds to ornithine decarboxylase (ODC), and targets it to rapid ubiquitin-independent degradation by the 26S proteasome. However, the metabolic fate of antizyme is not clear. We have tested the stability of antizyme in mammalian cells. In contrast with previous studies demonstrating stability in vitro in a reticulocyte lysate-based degradation system, in cells antizyme is rapidly degraded and this degradation is inhibited by specific proteasome inhibitors. . | Eur. J. Biochem. 269 1316-1322 2002 FEBS 2002 Ornithine decarboxylase-antizyme is rapidly degraded through a mechanism that requires functional ubiquitin-dependent proteolytic activity Shilpa Gandre Zippi Bercovich and Chaim Kahana Department of Molecular Genetics Weizmann Institute of Science Israel Antizyme is a polyamine-induced cellular protein that binds to ornithine decarboxylase ODC and targets it to rapid ubiquitin-independent degradation by the 26S proteasome. However the metabolic fate of antizyme is not clear. We have tested the stability of antizyme in mammalian cells. In contrast with previous studies demonstrating stability in vitro in a reticulocyte lysate-based degradation system in cells antizyme is rapidly degraded and this degradation is inhibited by specific proteasome inhibitors. While the degradation of ODC is stimulated by the presence of cotransfected antizyme degradation of antizyme seems to be independent of ODC suggesting that antizyme degradation does not occur while presenting ODC to the 26S protea-some. Interestingly both species of antizyme which represent initiation at two in-frame initiation codons are rapidly degraded. The degradation of both antizyme proteins is inhibited in ts20 cells containing a thermosensitive ubiquitin-activating enzyme E1. Therefore we conclude that in contrast with ubiquitin-independent degradation of ODC degradation of antizyme requires a functional ubiquitin system. Keywords antizyme ornithine decarboxylase protein degradation proteasome polyamines. The polyamines spermidine and spermine and their precursor putrescine are ubiquitous aliphatic polycations with multiple cellular functions. Polyamines were demonstrated to be essential for fundamental cellular processes such as growth differentiation transformation and apoptosis 1-5 although their explicit role in these cellular processes is mostly unknown. Nevertheless due to the critical role of polyamines in various cellular functions multiple pathways .