title: The COP9 signalosome counteracts the accumulation of cullin SCF ubiquitin E3 RING ligases during fungal development.
abstract: Defects in the COP9 signalosome (CSN) impair multicellular development, including embryonic plant or animal death or a block in sexual development of the fungus Aspergillus nidulans. CSN deneddylates cullin-RING ligases (CRLs), which are activated by covalent linkage to ubiquitin-like NEDD8. Deneddylation allows CRL disassembly for subsequent reassembly. An attractive hypothesis is a consecutive order of CRLs for development, which demands repeated cycles of neddylation and deneddylation for reassembling CRLs. Interruption of these cycles could explain developmental blocks caused by csn mutations. This predicts an accumulation of neddylated CRLs exhibiting developmental functions when CSN is dysfunctional. We tested this hypothesis in A. nidulans, which tolerates reduced levels of neddylation for growth. We show that only genes for CRL subunits or neddylation are essential, whereas CSN is primarily required for development. We used functional tagged NEDD8, recruiting all three fungal cullins. Cullins are associated with the CSN1/CsnA subunit when deneddylation is defective. Two CRLs were identified which are specifically involved in differentiation and accumulate during the developmental block. This suggests that an active CSN complex is required to counteract the accumulation of specific CRLs during development.
authors.affiliation: Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Grisebachstrasse 8, D-37077 Göttingen, Germany.
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: von Zeska Kress
authors.forename: Rebekka
authors.initials: R
authors.lastname: Harting
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Bayram
authors.forename: Martin
authors.initials: M
authors.lastname: Christmann
authors.forename: Henriette
authors.initials: H
authors.lastname: Irmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Valerius
authors.forename: Josua
authors.initials: J
authors.lastname: Schinke
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
mesh_terms: D001233:Aspergillus nidulans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D000075686:COP9 Signalosome Complex; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015966:Gene Expression Regulation, Fungal; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D044842:Cullin Proteins; D005656:Fungal Proteins; D046912:Multiprotein Complexes; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex