Antizyme affects cell proliferation and viability solely through regulating cellular

Antizymes are key regulators of the cellular polyamine metabolism that negatively regulate cellular proliferation and are therefore regarded as tumor suppressors. While the regulation of Az synthesis by polyamines and its ability to regulate cellular polyamine levels suggest the centrality of polyamine metabolism to its anti-proliferative function, recent studies have suggested that antizymes might also regulate cellular proliferation by targeting to degradation proteins that do not belong to the cellular polyamine metabolic pathway. Using a co-degradation assay we show here that while they efficiently stimulated the degradation of ODC, Az1 and Az2 did not affect or had negligible effect on the degradation of Cyclin D1, Aurora-A and a p73 variant lacking the N-terminal trans activation domain whose degradation was recently reported to be stimulated by Az1. Furthermore, we demonstrate that while Az1 and Az2 can not be constitutively expressed in transfected cells, they can be stably expressed in cells that express trypanosome ODC, a form of ODC that does not bind Az and therefore maintains a constant level of cellular polyamines. Taken together, our results clearly demonstrate that Az 1 and 2 affect cellular proliferation and viability solely by modulating cellular polyamine metabolism.