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F-box-directed CRL complex assembly and regulation by the CSN and CAND1.

The COP9 signalosome (CSN) is thought to maintain the stability of cullin-RING ubiquitin ligases (CRL) by limiting the autocatalytic destruction of substrate adapters such as F box proteins (FBPs). CAND1, a protein associated with unneddylated CUL1, was proposed to assist in this role in an as yet unclear fashion. We found that only a subset of Schizosaccharomyces pombe FBPs, which feature a critical F box proline that promotes their interaction with CUL1, required CSN for stability. Unlike the CRL3 adaptor Btb3p, none of the CSN-sensitive FBPs were affected by deletion of ubp12. Contrary to current models, CAND1 does not control adaptor stability but maintains the cellular balance of CRL1 complexes by preventing rare FBPs from being outcompeted for binding to CUL1 by more ample adapters. These findings were integrated into a refined model of CRL control in which substrate availability toggles CRLs between independent CSN and CAND1 cycles.

Pubmed ID: 19748355


  • Schmidt MW
  • McQuary PR
  • Wee S
  • Hofmann K
  • Wolf DA


Molecular cell

Publication Data

September 11, 2009

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM59780
  • Agency: NCI NIH HHS, Id: P30 CA030199
  • Agency: NIGMS NIH HHS, Id: R01 GM059780
  • Agency: NIGMS NIH HHS, Id: R01 GM059780-06
  • Agency: NIGMS NIH HHS, Id: R01 GM059780-07
  • Agency: NIGMS NIH HHS, Id: R01 GM059780-08
  • Agency: NIGMS NIH HHS, Id: R01 GM059780-09

Mesh Terms

  • Amino Acid Sequence
  • CDC2 Protein Kinase
  • Conserved Sequence
  • Cullin Proteins
  • Endopeptidases
  • F-Box Proteins
  • Metalloproteases
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Mutation
  • Peptide Hydrolases
  • Proline
  • Protein Binding
  • Protein Stability
  • SKP Cullin F-Box Protein Ligases
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Time Factors
  • Ubiquitins