Deneddylase 1 regulates deneddylase activity of the Cop9 signalosome in Drosophila melanogaster.
NEDD8 conjugation of Cullin has an important role in ubiquitin-mediated protein degradation. The COP9 signalosome, of which CSN5 is the major catalytic subunit, is a major Cullin deneddylase. Another deneddylase, Deneddylase 1, has also been shown to process the Nedd8 precursor. In Drosophila, the DEN1 mutants do not have increased levels of Cullin neddylation, but instead show a significant decrease in neddylated Cullin. This characteristic decrease in neddylated Cullins in the DEN1nullbackground can be rescued by UAS-dDEN1WToverexpression but not by overexpression of mature NEDD8, indicating that this phenotype is distinct from the NEDD8-processing function of DEN1. We examined the role of DEN1-CSN interaction in regulating Cullin neddylation. Overexpression of DEN1 in a CSN5hypobackground slightly reduced unneddylated Cullin levels. The CSN5, DEN1 double mutation partially rescues the premature lethality associated with the CSN5 single mutation. These results suggest that DEN1 regulates Cullin neddylation by suppressing CSN deneddylase activity.
Department of Medical Biotechnology, Soonchunhyang University, Asan, 336-745.
Kiyoung
K
Kim
Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Cheongwon, 361-951.
Jeongsook
J
Yoon
Department of Medical Biotechnology, Soonchunhyang University, Asan, 336-745.
Jeongbin
J
Yim
Department of Neural Development and Disease, Korea Brain Research Institute, Daegu, 701-300, Korea.
Hyung-Jun
HJ
Kim
D000818:Animals; D044842:Cullin Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011499:Protein Processing, Post-Translational; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D044842:Cullin Proteins; D029721:Drosophila Proteins; D014452:Ubiquitins; C000620846:DEN1 protein, Drosophila; D010450:Endopeptidases
COP9 signalosome; Cullin; DEN1; Drosophila; NEDD8