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Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins.

The modular SCF (Skp1, cullin, and F box) ubiquitin ligases feature a large family of F box protein substrate receptors that enable recognition of diverse targets. However, how the repertoire of SCF complexes is sustained remains unclear. Real-time measurements of formation and disassembly indicate that SCF(Fbxw7) is extraordinarily stable, but, in the Nedd8-deconjugated state, the cullin-binding protein Cand1 augments its dissociation by one-million-fold. Binding and ubiquitylation assays show that Cand1 is a protein exchange factor that accelerates the rate at which Cul1-Rbx1 equilibrates with multiple F box protein-Skp1 modules. Depletion of Cand1 from cells impedes recruitment of new F box proteins to pre-existing Cul1 and profoundly alters the cellular landscape of SCF complexes. We suggest that catalyzed protein exchange may be a general feature of dynamic macromolecular machines and propose a hypothesis for how substrates, Nedd8, and Cand1 collaborate to regulate the cellular repertoire of SCF complexes.

Pubmed ID: 23453757

Authors

  • Pierce NW
  • Lee JE
  • Liu X
  • Sweredoski MJ
  • Graham RL
  • Larimore EA
  • Rome M
  • Zheng N
  • Clurman BE
  • Hess S
  • Shan SO
  • Deshaies RJ

Journal

Cell

Publication Data

March 28, 2013

Associated Grants

  • Agency: PHS HHS, Id: 10565784
  • Agency: NCI NIH HHS, Id: CA138126
  • Agency: NIGMS NIH HHS, Id: GM065997
  • Agency: NCI NIH HHS, Id: R01 CA084069
  • Agency: NIGMS NIH HHS, Id: R01 GM065997
  • Agency: NCI NIH HHS, Id: T32 CA080416
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Cell Line
  • Cullin Proteins
  • Escherichia coli
  • F-Box Proteins
  • Humans
  • Mass Spectrometry
  • SKP Cullin F-Box Protein Ligases
  • Transcription Factors