NEDD8 recruits E2-ubiquitin to SCF E3 ligase.
NEDD8/Rub1 is a ubiquitin (Ub)-like post-translational modifier that is covalently linked to cullin (Cul)-family proteins in a manner analogous to ubiquitylation. NEDD8 is known to enhance the ubiquitylating activity of the SCF complex (composed of Skp1, Cul-1, ROC1 and F-box protein), but the mechanistic role is largely unknown. Using an ... in vitro reconstituted system, we report here that NEDD8 modification of Cul-1 enhances recruitment of Ub-conjugating enzyme Ubc4 (E2) to the SCF complex (E3). This recruitment requires thioester linkage of Ub to Ubc4. Our findings indicate that the NEDD8-modifying system accelerates the formation of the E2-E3 complex, which stimulates protein polyubiquitylation.
Mesh Terms:
Cell Line, DNA-Binding Proteins, Humans, I-kappa B Proteins, Ligases, Peptide Synthases, SKP Cullin F-Box Protein Ligases, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitins
Cell Line, DNA-Binding Proteins, Humans, I-kappa B Proteins, Ligases, Peptide Synthases, SKP Cullin F-Box Protein Ligases, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitins
EMBO J.
Date: Aug. 01, 2001
PubMed ID: 11483504
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