[Mechanisms of degradation of the fungal ornithine decarboxylase].
Ornithine decarboxylase (ODC) is the first enzyme in polyamine biosynthesis in numerous living organisms, from bacteria to mammalian cells. Its control is under negative feedback regulation by the end products of the pathway. In dimorphic fungi, ODC activity and therefore polyamine concentrations are related to the morphogenetic process. From the fission yeast Schizosaccharomyces pombe to human, polyamines induce antizyme synthesis which in turn inactivates ODC. This is hydrolyzed by the 26S proteasome without ubiquitination. The regulatory mechanism of antizyme on polyamines is conserved, although to date no antizyme homology has been identified in some fungal species. The components that are responsible for regulating polyamine levels in cells and the current knowledge of ODC regulation in dimorphic fungi are presented in this review. ODC degradation is of particular interest because inhibitors of this pathway may lead to the discovery of novel antifungal drugs.
Sorais
Françoise
F
Instituto Venezolano de Investigaciones Científicas, Centro de Microbiología y Biología Celular, Caracas, Venezuela.
Niño-Vega
Gustavo
G
San-Blas
Gioconda
G
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004789:Enzyme Activation; D025461:Feedback, Physiological; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism; D009024:Morphogenesis; D009090:Mucorales / Q000201:enzymology / Q000254:growth & development; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010228:Paracoccidioides / Q000201:enzymology / Q000254:growth & development; D010447:Peptide Hydrolases / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D013045:Species Specificity
D029721:Drosophila Proteins; D005656:Fungal Proteins; D011073:Polyamines; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C031017:ornithine decarboxylase antizyme; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D009955:Ornithine Decarboxylase