Antizyme

Abstract

Antizyme (AZ) first emerged as an inhibitor of ornithine decarboxylase (ODC), a key enzyme in the polyamine biosynthesis. Expression of AZ rises in response to increasing cellular polyamine levels through the polyamine-induced translational frameshifting mechanism. Synthesized AZ proteins bind to an ODC monomer and trigger its degradation by the 26S proteasome in a ubiquitin- independent manner. To reduce the cellular polyamine level, AZ also inhibits the uptake of extracellular polyamine. Therefore, AZ provides the feedback regulation of cellular polyamines. In mammals, cells express three members of the AZ protein family: AZ1-3, AZ1, and AZ2, are distributed in most tissues whereas AZ3 is testis specific. AZ is regulated by protein antizyme inhibitors (AZINs) that are homologous to ODC but lack the enzymatic activity. Two isoforms of AZINs, AZIN1 and AZIN2, are known. This chapter reviews the function and regulation of AZs and AZINs.