Polyamines in spermiogenesis: not now, darling.

I processes invariably employ interesting biochemistry,” declares Marc Kirschner (1). From this statement, one may readily conclude that antizyme (AZ) deserves our attention. AZ is the central element in a feedback loop that controls cellular polyamines. AZ is interesting for a number of reasons. First, AZ production requires the exercise of a remarkable mechanism, translational frameshifting. Second, AZ has the unique ability to cause proteasomal degradation of a protein target without using ubiquitin, thereby evoking another Kirschnerian dictum: Labile proteins are important and important proteins are labile. First identified as an inducible biochemical activity that inhibits a specific enzyme target (2), recent developments have deepened our understanding of AZ biochemistry and physiology and broadened our appreciation of the AZs as a protein family conserved in structure and means of production. In this issue of PNAS, Ivanov et al. (3) describe a novel AZ family member, termed AZ3. It is expressed only in the testes and is there restricted to the postmeiotic stages of spermatogenesis. Tosaka et al. have independently described similar findings (4), using a gene (they term OAZ-t) cloned from a haploid-germ-cellspecific library. The pattern of AZ3 expression suggests that it acts to sharply limit polyamine accumulation in cells that have finished DNA synthesis and meiotic reduction and are about to be remodeled into mature spermatozoa. The reported observations imply a need for adroit control of polyamines in spermatogenesis.