The COP9 signalosome counteracts the accumulation of cullin SCF ubiquitin E3 RING ligases during fungal development

von Zeska Kress, Marcia Regina and Harting, Rebekka and Bayram, Ozgur and Christmann, Martin and Irmer, Henriette and Valerius, Oliver and Schinke, Josua and Goldman, Gustavo H. and Braus, Gerhard H. (2012) The COP9 signalosome counteracts the accumulation of cullin SCF ubiquitin E3 RING ligases during fungal development. Molecular Microbiology, 83 (6). pp. 1162-1177. ISSN 0950-382X

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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.

Item Type: Article
Keywords: COP9; signalosome; accumulation; cullin SCF ubiquitin E3 RING ligases; fungal development; cullin-RING ligases;
Academic Unit: Faculty of Science and Engineering > Biology
Item ID: 7178
Identification Number: 10.1111/j.1365-2958.2012.07999
Depositing User: Ozgur Bayram
Date Deposited: 08 Jul 2016 15:18
Journal or Publication Title: Molecular Microbiology
Publisher: Blackwell Publishing Ltd.
Refereed: Yes

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