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

Nathan W Pierce, J Eugene Lee, Xing Liu, Michael J Sweredoski, Robert L J Graham, Elizabeth A Larimore, Michael Rome, Ning Zheng, Bruce E Clurman, Sonja Hess, Shu-ou Shan, Raymond J Deshaies

Research output: Contribution to journalArticlepeer-review

151 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)206-15
Number of pages10
JournalCell
Volume153
Issue number1
DOIs
Publication statusPublished - 28 Mar 2013

Keywords

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

Fingerprint

Dive into the research topics of 'Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins'. Together they form a unique fingerprint.

Cite this