title: The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development.
abstract: DenA/DEN1 and the COP9 signalosome (CSN) represent two deneddylases which remove the ubiquitin-like Nedd8 from modified target proteins and are required for distinct fungal developmental programmes. The cellular DenA/DEN1 population is divided into a nuclear and a cytoplasmatic subpopulation which is especially enriched at septa. DenA/DEN1 stability control mechanisms are different for the two cellular subpopulations and depend on different physical interacting proteins and the C-terminal DenA/DEN1 phosphorylation pattern. Nuclear DenA/DEN1 is destabilized during fungal development by five of the eight CSN subunits which target nuclear DenA/DEN1 for degradation. DenA/DEN1 becomes stabilized as a phosphoprotein at S243/S245 during vegetative growth, which is necessary to support further asexual development. After the initial phase of development, the newly identified cytoplasmatic DenA/DEN1 interacting phosphatase DipA and an additional developmental specific C-terminal phosphorylation site at serine S253 destabilize DenA/DEN1. Outside of the nucleus, DipA is co-transported with DenA/DEN1 in the cytoplasm between septa and nuclei. Deletion of dipA resulted in increased DenA/DEN1 stability in a strain which is unresponsive to illumination. The mutant strain is dysregulated in cytokinesis and impaired in asexual development. Our results suggest a dual phosphorylation-dependent DenA/DEN1 stability control with stabilizing and destabilizing modifications and physical interaction partner proteins which function as control points in the nucleus and the cytoplasm.
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Josua
authors.initials: J
authors.lastname: Schinke
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kolog Gulko
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Christmann
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Valerius
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Sina Kristin
authors.initials: SK
authors.lastname: Stumpf
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Margarita
authors.initials: M
authors.lastname: Stirz
authors.affiliation: Department of Molecular Microbiology and Genetics, Göttingen Center for Molecular Biosciences (GZMB), and Georg-August-University, Göttingen, Germany.
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics* / Q000254:growth & development; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D046912:Multiprotein Complexes; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D025801:Ubiquitin; D014452:Ubiquitins; C000609520:DipA protein, Aspergillus nidulans; D010744:Phosphoric Monoester Hydrolases; D010450:Endopeptidases; C000609518:DEN1 protein, Aspergillus nidulans