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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.
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