Nuclear translocation of antizyme and expression of ornithine decarboxylase and antizyme are developmentally regulated

The polyamines are important regulators of cell growth and differentiation. Cells acquire polyamines by energy-dependent transport and by synthesis wh ere the highly regulated ornithine decarboxylase (ODC) catalyzes the first and rate-controlling step. Inactivation of ODC is mainly exerted by antizym e (AZ), a 20-25 kDa polyamine-induced protein that binds to ODC, inactivate s it, and targets it for degradation by the 26S proteasome without ubiquiti nation, In the present study, we have performed a systematic analysis of th e expression of ODC and AZ, at the mRNA and protein levels, during mouse de velopment, The expression patterns for ODC and AZ were found to be developm entally regulated, suggesting important functions for the polyamines in ear ly embryogenesis, axonogenesis, epithelial-mesenchymal interaction, and in apoptosis. In addition, AZ protein was found to translocate to the nucleus in a developmentally regulated manner. The nuclear localization is consiste nt with the fact that the amino acid sequence of AZ exhibits features that characterize nuclear proteins. Interestingly, we found that cultivation of mandibular components of the first branchial arch in the presence of a sele ctive proteasome inhibitor caused ODC accumulation in the nucleus of a subs et of cells, suggesting that the observed nuclear translocation of AZ is li nked to proteasome-mediated ODC degradation in the nucleus. The presence of AZ in the nucleus may suggest that nuclear ODC activity is under tight con trol, and that polyamine production can be rapidly interrupted when those d evelopmental events, which depend on access to nuclear polyamines, have kee n completed. (C) 2001 Wiley-Liss, Inc.