NEDD8 Modification of CUL1 Dissociates p120(CAND1), an Inhibitor of CUL1-SKP1 Binding and SCF Ligases

Mol Cell. 2002 Dec;10(6):1511-8. doi: 10.1016/s1097-2765(02)00783-9.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cullin Proteins*
  • DNA-Binding Proteins*
  • Enzyme Inhibitors / metabolism*
  • F-Box Proteins*
  • Genes, myc
  • Humans
  • Kinetics
  • Ligases / metabolism
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • NEDD8 Protein
  • Peptide Synthases / antagonists & inhibitors*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • SKP Cullin F-Box Protein Ligases
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors*
  • Ubiquitins / metabolism*

Substances

  • Bacterial Proteins
  • CAND1 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cullin 1
  • Cullin Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • F-Box Proteins
  • Macromolecular Substances
  • NEDD8 Protein
  • NEDD8 protein, human
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ubiquitins
  • SKP Cullin F-Box Protein Ligases
  • SKP1 protein, S cerevisiae
  • Ligases
  • Peptide Synthases