title: Control of multicellular development by the physically interacting deneddylases DEN1/DenA and COP9 signalosome.
abstract: Deneddylases remove the ubiquitin-like protein Nedd8 from modified proteins. An increased deneddylase activity has been associated with various human cancers. In contrast, we show here that a mutant strain of the model fungus Aspergillus nidulans deficient in two deneddylases is viable but can only grow as a filament and is highly impaired for multicellular development. The DEN1/DenA and the COP9 signalosome (CSN) deneddylases physically interact in A. nidulans as well as in human cells, and CSN targets DEN1/DenA for protein degradation. Fungal development responds to light and requires both deneddylases for an appropriate light reaction. In contrast to CSN, which is necessary for sexual development, DEN1/DenA is required for asexual development. The CSN-DEN1/DenA interaction that affects DEN1/DenA protein levels presumably balances cellular deneddylase activity. A deneddylase disequilibrium impairs multicellular development and suggests that control of deneddylase activity is important for multicellular development.
authors: Department of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, Göttingen, Germany.
authors: Martin
authors: M
authors: Christmann
authors: Tilo
authors: T
authors: Schmaler
authors: Colin
authors: C
authors: Gordon
authors: Xiaohua
authors: X
authors: Huang
authors: Ozgür
authors: O
authors: Bayram
authors: Josua
authors: J
authors: Schinke
authors: Sina
authors: S
authors: Stumpf
authors: Wolfgang
authors: W
authors: Dubiel
authors: Gerhard H
authors: GH
authors: Braus
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics / Q000254:growth & development; D000075686:COP9 Signalosome Complex; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D000075687:NEDD8 Protein; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins; D010450:Endopeptidases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; C477008:SENP8 protein, human