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Cell. 2013 Mar 28;153(1):206-15. doi: 10.1016/j.cell.2013.02.024. Epub 2013 Feb 28.

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

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1
Division of Biology, MC 156-29, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.

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.

PMID:
23453757
PMCID:
PMC3656483
DOI:
10.1016/j.cell.2013.02.024
[Indexed for MEDLINE]
Free PMC Article
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