title: Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase.
abstract: ODC (ornithine decarboxylase), the rate-limiting enzyme in polyamine biosynthesis, is regulated by specific inhibitors, AZs (antizymes), which in turn are inhibited by AZI (AZ inhibitor). We originally identified and cloned the cDNA for a novel human ODC-like protein called ODCp (ODC paralogue). Since ODCp was devoid of ODC catalytic activity, we proposed that ODCp is a novel form of AZI. ODCp has subsequently been suggested to function either as mammalian ADC (arginine decarboxylase) or as AZI in mice. Here, we report that human ODCp is a novel AZI (AZIN2). By using yeast two-hybrid screening and in vitro binding assay, we show that ODCp binds AZ1-3. Measurements of the ODC activity and ODC degradation assay reveal that ODCp inhibits AZ1 function as efficiently as AZI both in vitro and in vivo. We further demonstrate that the degradation of ODCp is ubiquitin-dependent and AZ1-independent similar to the degradation of AZI. We also show that human ODCp has no intrinsic ADC activity.
authors: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Kristiina
authors: K
authors: Kanerva
authors: Laura T
authors: LT
authors: Mäkitie
authors: Anna
authors: A
authors: Pelander
authors: Marja
authors: M
authors: Heiskala
authors: Leif C
authors: LC
authors: Andersson
mesh_terms: D000818:Animals; D019556:COS Cells; D002262:Carboxy-Lyases / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009955:Ornithine Decarboxylase / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D018076:DNA, Complementary; D025801:Ubiquitin; D005982:Glutathione Transferase; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; C019722:arginine decarboxylase