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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Bacterial Proteins / antagonists & inhibitors
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / metabolism*
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Cullin Proteins*
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DNA-Binding Proteins*
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Enzyme Inhibitors / metabolism*
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F-Box Proteins*
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Genes, myc
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Humans
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Kinetics
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Ligases / metabolism
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Macromolecular Substances
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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NEDD8 Protein
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Peptide Synthases / antagonists & inhibitors*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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SKP Cullin F-Box Protein Ligases
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins*
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Transcription Factors*
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Ubiquitins / metabolism*
Substances
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Bacterial Proteins
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CAND1 protein, human
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Carrier Proteins
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Cell Cycle Proteins
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Cullin 1
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Cullin Proteins
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DNA-Binding Proteins
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Enzyme Inhibitors
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F-Box Proteins
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Macromolecular Substances
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NEDD8 Protein
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NEDD8 protein, human
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Ubiquitins
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SKP Cullin F-Box Protein Ligases
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SKP1 protein, S cerevisiae
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Ligases
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Peptide Synthases