Distinct domains of antizyme required for binding and proteolysis of ornithine decarboxylase.
Selective degradation by proteasomes of ornithine decarboxylase, the initial enzyme in polyamine biosynthesis, is mediated by the polyamine-inducible protein antizyme. Antizyme binds to a region near the N terminus of ornithine decarboxylase (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-3562, 1992). This interaction induces a conformational change in ornithine decarboxylase that exposes its C terminus and inactivates the enzyme (X. Li and P. Coffino, Mol. Cell. Biol. 13:1487-1492, 1993). Here we show that the C-terminal half of antizyme alone can inactivate ornithine decarboxylase and alter its conformation, but it cannot direct degradation of the enzyme, either in vitro or in vivo. A portion of the N-terminal half of antizyme must be present to promote degradation.
Li
X
X
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Coffino
P
P
D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004795:Enzyme Stability; D051379:Mice; D016296:Mutagenesis; D009955:Ornithine Decarboxylase / Q000737:chemistry / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D018076:DNA, Complementary; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011506:Proteins; D011993:Recombinant Fusion Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase