title: Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins.
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.
authors: Division of Biology, MC 156-29, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors: Nathan W
authors: NW
authors: Pierce
authors: J Eugene
authors: JE
authors: Lee
authors: Xing
authors: X
authors: Liu
authors: Michael J
authors: MJ
authors: Sweredoski
authors: Robert L J
authors: RL
authors: Graham
authors: Elizabeth A
authors: EA
authors: Larimore
authors: Michael
authors: M
authors: Rome
authors: Ning
authors: N
authors: Zheng
authors: Bruce E
authors: BE
authors: Clurman
authors: Sonja
authors: S
authors: Hess
authors: Shu-ou
authors: SO
authors: Shan
authors: Raymond J
authors: RJ
authors: Deshaies
mesh_terms: D000818:Animals; D002460:Cell Line; D044842:Cullin Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D044783:F-Box Proteins / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D044843:SKP Cullin F-Box Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C486317:CAND1 protein, human; C100318:Cullin 1; D044842:Cullin Proteins; D044783:F-Box Proteins; D014157:Transcription Factors; D044843:SKP Cullin F-Box Protein Ligases