title: Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.
abstract: SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits--including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lyapina
authors.forename: G
authors.initials: G
authors.lastname: Cope
authors.forename: A
authors.initials: A
authors.lastname: Shevchenko
authors.forename: G
authors.initials: G
authors.lastname: Serino
authors.forename: T
authors.initials: T
authors.lastname: Tsuge
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.forename: D A
authors.initials: DA
authors.lastname: Wolf
authors.forename: N
authors.initials: N
authors.lastname: Wei
authors.forename: A
authors.initials: A
authors.lastname: Shevchenko
authors.forename: R J
authors.initials: RJ
authors.lastname: Deshaies
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D044842:Cullin Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D046912:Multiprotein Complexes; D009154:Mutation / Q000235:genetics; D000075687:NEDD8 Protein; D010447:Peptide Hydrolases; D010453:Peptide Synthases / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D005656:Fungal Proteins; D046912:Multiprotein Complexes; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C513172:Nedd8 protein, mouse; D021122:Protein Subunits; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D010453:Peptide Synthases