title: Polyamine-independent Expression of Caenorhabditis elegans Antizyme.
abstract: Degradation of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis, is promoted by the protein antizyme. Expression of antizyme is positively regulated by rising polyamine concentrations that induce a +1 translational frameshift required for production of the full-length protein. Antizyme itself is negatively regulated by the antizyme inhibitor. In our study, the regulation of Caenorhabditis elegans antizyme was investigated, and the antizyme inhibitor was identified. By applying a novel GFP-based method to monitor antizyme frameshifting in vivo, we show that the induction of translational frameshifting also occurs under stressful conditions. Interestingly, during starvation, the initiation of frameshifting was independent of polyamine concentrations. Because frameshifting was also prevalent in a polyamine auxotroph double mutant, a polyamine-independent regulation of antizyme frameshifting is suggested. Polyamine-independent induction of antizyme expression was found to be negatively regulated by the peptide transporter PEPT-1, as well as the target of rapamycin, but not by the daf-2 insulin signaling pathway. Stress-dependent expression of C. elegans antizyme occurred morely slowly than expression in response to increased polyamine levels, pointing to a more general reaction to unfavorable conditions and a diversion away from proliferation and reproduction toward conservation of energy. Interestingly, antizyme expression was found to drastically increase in aging individuals in a postreproductive manner. Although knockdown of antizyme did not affect the lifespan of C. elegans, knockdown of the antizyme inhibitor led to a significant reduction in lifespan. This is most likely caused by an increase in antizyme-mediated degradation of ornithine decarboxylase-1 and a resulting reduction in cellular polyamine levels.
authors.affiliation: Department of Molecular Physiology, Institute for Animal Physiology, University of Muenster, 48143 Muenster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Stegehake
authors.affiliation: Department of Molecular Physiology, Institute for Animal Physiology, University of Muenster, 48143 Muenster, Germany.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Kurosinski
authors.affiliation: Department of Molecular Physiology, Institute for Animal Physiology, University of Muenster, 48143 Muenster, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schürmann
authors.affiliation: Department of Molecular Physiology, Institute for Animal Physiology, University of Muenster, 48143 Muenster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Daniel
authors.affiliation: Department of Molecular Physiology, Institute for Animal Physiology, University of Muenster, 48143 Muenster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Lüersen
authors.affiliation: Department of Molecular Physiology, Institute for Animal Physiology, University of Muenster, 48143 Muenster, Germany. Electronic address: liebaue@uni-muenster.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Liebau
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D018965:Frameshifting, Ribosomal; D008136:Longevity; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D059748:Proteolysis; D012098:Reproduction; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase
keywords: Caenorhabditis elegans (C. elegans); antizyme; antizyme inhibitor; frameshifting; odc; ornithine decarboxylase; polyamine; spermidine; stress; stress response