NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases.
Journal:
Mol. Cell 2002 DecAuthors:
Liu J, Furukawa M, Matsumoto T, Xiong Y
Abstract
Cullin proteins assemble a large number of RING E3 ubiquitin ligases and regulate various physiological processes. Covalent modification of cullins by the ubiquitin-like protein NEDD8 activates cullin ligases through an as yet undefined mechanism. We show here that p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation. CAND1 formed a ternary complex with CUL1 and ROC1. CAND1 dissociated SKP1 from CUL1 and inhibited SCF ligase activity in vitro. Suppression of
...[more]CAND1 in vivo increased the level of the CUL1-SKP1 complex. We suggest that by restricting SKP1-CUL1 interaction, CAND1 regulated the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes.[less]
Mesh Headings:
Amino Acid Sequence, Bacterial Proteins, Carrier Proteins, Cell Cycle Proteins, Cullin Proteins, DNA-Binding Proteins, Enzyme Inhibitors, F-Box Proteins, Genes, myc, Humans, Kinetics, Ligases, Macromolecular Substances, Molecular Sequence Data, Mutagenesis, Site-Directed, Peptide Synthases, Recombinant Proteins, SKP Cullin F-Box Protein Ligases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Ubiquitins