title: Intracellular localization of ornithine decarboxylase and its regulatory protein, antizyme-1.
abstract: The enzyme ornithine decarboxylase (ODC) and its regulatory protein antizyme-1 (AZ1) are key regulators in the homeostasis of polyamines. To gain more insight into the exact intracellular distribution of ODC and AZ1, we performed immunocytochemical and Green Fluorescent Protein-fluorocytochemical studies in cultured human cervix carcinoma and human prostatic carcinoma (PC-346C) cells. ODC localization patterns varied from predominantly cytoplasmic to both cytoplasmic and nuclear staining, whereas AZ1 was mostly found in the nucleus. In cells that were synchronized in the mitotic phase, localization of both ODC and AZ1 changed from perinuclear at the beginning of mitosis into nucleoplasmic at close proximity to the chromosomes during meta-, ana- and telophase. Upon completion of mitosis, localization of ODC and AZ1 was reverted back to the cytoplasm, i.e., predominantly perinuclear immediately after cytokinesis. When PC-346C cells were treated with polyamines to induce AZ1-regulated ODC degradation, ODC was predominantly found in the nucleus and colocalized with immunoreactive AZ1. A comparable accumulation of ODC and AZ1 in the nucleus was found in PC-346C cells treated with the polyamine analog SL-11093. The present study suggests that AZ1 is involved in nucleocytoplasmic shuttling of ODC, which may be a prerequisite for ODC regulation and/or function.
authors.affiliation: Department of Pathology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Schipper
authors.forename: Vincent M J I
authors.initials: VM
authors.lastname: Cuijpers
authors.forename: Linda H J M
authors.initials: LH
authors.lastname: De Groot
authors.forename: Marco
authors.initials: M
authors.lastname: Thio
authors.forename: Albert A J
authors.initials: AA
authors.lastname: Verhofstad
mesh_terms: D045744:Cell Line, Tumor; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics; D008938:Mitosis; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: C475839:3,8,13,18-tetraaza-10,11-((E)-1,2-cyclopropyl)eicosane tetrahydrochloride; D008164:Luminescent Proteins; D011073:Polyamines; D011506:Proteins; D011993:Recombinant Fusion Proteins; C031017:ornithine decarboxylase antizyme; D049452:Green Fluorescent Proteins; D009955:Ornithine Decarboxylase; D011700:Putrescine