ABSTRACT

Posttranslational control of the enzyme o rn ith ine decarboxylase (ODC) employs unusual mechanisms. The proteasome degrades ODC, but ubiquitin is not involved in this process. ODC degradation is instead controlled by the protein antizyme (AZ). This interaction, resulting in the destruction of ODC and the recycling of AZ, is an elem ent o f a novel and complex mechanism of feedback regulation, which limits cellular accumulation of the downstream products of ODC, the polyamines. The elements of this feedback loop are as follows: ODC is the initial enzyme in the biosynthesis of polyamines, small essential abundant molecules ubiquitous in living organisms. When cellular levels of polyamines rise, the synthesis of AZ is stimulated. Decoding the AZ mRNA requires translational frameshifting; polyamines make the required +1 frameshift more efficient. Increased AZ leads to destruction of ODC, thereby lim iting polyamine production. The remainder of this chapter will describe these events in greater detail.