PathwayStep2540 PathwayStep2539 PathwayStep2538 PathwayStep2537 Regulation of ornithine decarboxylase (ODC) Authored: Gopinathrao, G, 2008-05-19 18:50:15 GENE ONTOLOGYGO:0006521 Polyamines increase the production of antizyme (AZ). The carboxy-terminal half of antizyme interacts with ODC, generating an inactive AZ:ODC heterodimer complex. A carboxy-terminal domain of ODC is exposed only within the heterodimer, and is the target for subsequent degradation. A domain within the amino-terminal portion of antizyme provides a function needed for efficient degradation of ODC by the proteasome. <br>The proteasome cycle starts with the processing of AZ:ODC, sequestering ODC and then degrading it to peptides but releasing AZ. AZ participates in additional rounds of binding and degradation. Antizyme-mediated inhibition and destruction of ODC reduces synthesis of polyamines. Additionally, antizyme also inhibits polyamine transport into the cell. Antizyme production is reduced, completing the regulatory circuit (Coffino, 2001).<br>The following illustration is adapted from a minireview by Pegg, 2006; J. Biol. Chem., Vol. 281, Issue 21, 14529-14532. Pubmed10623564 Pubmed11265248 Pubmed16205122 Pubmed16459331 Reactome Database ID Release 43350562 Reactome, http://www.reactome.org ReactomeREACT_13565 Reviewed: D'Eustachio, P, 2008-06-12 17:57:32 Antizyme OAZ binds to Ornithine decarboxylase NQO1 interaction with ODC 26S proteosome degrades ODC holoenzyme complex Antizyme inhibitor binds to OAZ and stablizes ODC complex