Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein.
Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis.
Li
X
X
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Coffino
P
P
D000818:Animals; D001665:Binding Sites; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism* / Q000648:ultrastructure; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000201:enzymology
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011506:Proteins; D011993:Recombinant Fusion Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase