The COP9 signalosome (CSN) is a conserved complex that is involved in ubiquitin-proteasome mediated protein degradation. Recently it has been observed that the CSN is physically associated with cullin-containing E3 ubiquitin ligases and possesses a deneddylation activity for the ubiquitin-like NEDD8 conjugated cullins. Cycles of neddylation and deneddylation are important for regulated protein degradation by the ubiquitin proteasome system; however, the precise role of the neddylation and deneddylation in cell function is unclear. In order to elucidate the physiological consequences of neddylation and deneddylation, I propose to use Arabidopsis as my model system. Mutant strains will be created that are defective for deneddylation activity but maintain an intact CSN complex, and their biochemical and developmental properties will be compared to csn null mutants and wild type. These mutants will be: catalytically defective for deneddylation or defective in the interaction between the CSN and either all cullin-based ubiquitin ligases or a specific subset, cullin1-containing E3 ligases. These studies will provide critical insights toward the mechanism of CSN function in regulating ubiquitylation and protein degradation.
