Portal de Periódicos da CAPES

Cand1 Promotes Assembly of New SCF Complexes through Dynamic Exchange of F Box Proteins

2013; Cell Press; Volume: 153; Issue: 1 Linguagem: Inglês

10.1016/j.cell.2013.02.024

1097-4172

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

Hippo pathway signaling and YAP/TAZ

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.