Regulated degradation of ornithine decarboxylase requires interaction with the polyamine-inducible protein antizyme.
Intracellular degradation of vertebrate ornithine decarboxylase (ODC) is accelerated by polyamines, the products of the pathway controlled by ODC. Antizyme, a reversible, tightly binding protein inhibitor of ODC activity, is believed to be involved in this process. Mouse and Trypanosoma brucei ODCs are structurally similar, but the trypanosome enzyme, unlike that of the mouse, is not regulated by intracellular polyamines when expressed in hamster cells (L. Ghoda, D. Sidney, M. Macrae, and P. Coffino, Mol. Cell. Biol. 12:2178-2185, 1992). We found that mouse ODC interacts with antizyme in vitro but trypanosome ODC does not. To localize the region necessary for binding, we made a series of enzymatically active chimeric mouse-trypanosome ODCs and tested them for antizyme interaction. Replacing residues 117 to 140 within the 461-amino-acid mouse ODC sequence with the equivalent region of trypanosome ODC disrupted both antizyme binding and in vivo regulation. Formation of an antizyme-ODC complex is therefore required for regulated degradation.
Li
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Department of Microbiology and Immunology, University of California, San Francisco 94143.
Coffino
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P
D000595:Amino Acid Sequence; D000818:Animals; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000201:enzymology
D011073:Polyamines; D011506:Proteins; D011994:Recombinant Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase