Antizyme, a mediator of ubiquitin-independent proteasomal degradation

Ornithine decarboxylase (ODC) is among the small set of proteasome substrat es that is not ubiquitinated. It is instead degraded in conjunction with th e protein antizyme (AZ). ODC and AZ are participants in a regulatory circui t that restricts pools of polyamines, the downstream products of ODC enzyma tic activity. Functional studies using directed mutagenesis have identified regions of ODC and AZ required for the process of ODC degradation. Within ODC, there is a region that is required for AZ binding which lies on the su rface of an alpha-beta barrel forming one domain of the ODC monomer. A carb oxy-terminal ODC domain is needed for both AZ-dependent and AZ-independent degradation. Within AZ, the carboxy-terminal half molecule is sufficient fo r binding to ODC, but an additional domain found within the AZ amino termin us must be present for stimulation of ODC degradation by the proteasome. Re cently, the AZs have been found to consist of an ancient gene family. Withi n vertebrate species, multiple isoforms are found, with distinct functions that remain to be sorted out. Although AZ homologs have been found in some yeast species, homology searches have failed to identify an AZ homolog in S accharomyces cerevisiae. Nevertheless, the close parallel between polyamine -induced ODC degradation in S. cerevisiae and in animal cells suggests that this organism will also be found to harbor an AZ-like protein. (C) 2001 So ciete francaise de biochimie et biologie moleculaire / Editions scientifiqu es et medicales Elsevier SAS. All rights reserved.