title: Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity.
abstract: Although cullin-1 neddylation is crucial for the activation of SCF ubiquitin E3 ligases, the underlying mechanisms for NEDD8-mediated activation of SCF remain unclear. Here we demonstrate by NMR and mutational studies that NEDD8 binds the ubiquitin E2 (UBC4), but not NEDD8 E2 (UBC12). Our data imply that NEDD8 forms an active platform on the SCF complex for selective recruitment of ubiquitin-charged E2s in collaboration with RBX1, and thereby upregulates the E3 activity.
authors.affiliation: Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Sakata
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saeki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsuda
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000737:chemistry*; D044842:Cullin Proteins / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D000075687:NEDD8 Protein; D025821:Polyubiquitin / Q000737:chemistry; D011485:Protein Binding; D044843:SKP Cullin F-Box Protein Ligases / Q000737:chemistry*; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C479529:RBX1 protein, human; D014452:Ubiquitins; D025821:Polyubiquitin; D044843:SKP Cullin F-Box Protein Ligases