Ornithine decarboxylase antizyme - Its structure, role, regulation, and comparative biochemistry

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Ornithine decarboxylase (ODC) antizyme is a unique regulatory protein involved in feedback inhibition and possibly degradation of the enzyme. Following results were obtained in this second year of supported research.(1) Determination of base sequence of antizyme MRNASequence analysis of newly cloned CDNA and genomic DNA indicated that rat liver antizyme is consisted of 227 amino acids and that translation of antizyme MRNA is likely to involve a frame-shift, a very unusual process in bukaryotic cells. (Matsufuji)(2) Tissue distribution of antizyme MRNANorthern blot analysis demonstrated that a single species of antizyme MRNA of 1.3 kb was widely and amply distributed in various murine tissues. The MRNA was quite stable in vivo (T_<1/2> = 12 h) and its amount did not increase upon putrescine treatment, indicating that the induction of antizyme by polyamines is due to translational stimulation. (Matsufuji)Role of antizymeProtein synthesis inhibitors like emetine and pactamycin inhibited antizyme synthesis as well as polyamine-caused acceleration of ODC decay, while amino acid analogs like ethionine and 5-fluorotryptophan inhibited neither antizyme induction nor polyamine-caused acceleration of ODC decay, indicating a close relationship between these two processes. An antizyme overproducing variant cell line was obtained from ODC-overproducing CHO cells. Studies on half-lives of free and antizyme-bound ODC in this cell line strongly suggested antizyme-mediated degradation of ODC. (Murakami)(4) Presence and role of antizyme in the frog Xenopus laevisInduction of antizyme and acceleration of ODC decay were both observed in primary cultured frog hepatocytes. (Hayashi & Murakami)