Control of Multicellular Development by the Physically Interacting Deneddylases DEN1/DenA and COP9 Signalosome

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. © 2013 christmann et al.