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

Pierce, Nathan W. and Lee, J. Eugene and Liu, Xing and Sweredoski, Michael J. and Graham, Robert L. J. and Larimore, Elizabeth A. and Rome, Michael and Zheng, Ning and Clurman, Bruce E. and Hess, Sonja and Shan, Shu-ou and Deshaies, Raymond J. (2013) Cand1 Promotes Assembly of New SCF Complexes through Dynamic Exchange of F Box Proteins. Cell, 153 (1). pp. 206-215. ISSN 0092-8674. PMCID PMC3656483. doi:10.1016/j.cell.2013.02.024.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Liu, Xing0000-0002-0506-6821
Sweredoski, Michael J.0000-0003-0878-3831
Hess, Sonja0000-0002-5904-9816
Shan, Shu-ou0000-0002-6526-1733
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2013 Elsevier Inc. Received: December 10, 2012. Revised: January 24, 2013. Accepted: February 12, 2013. Published: February 28, 2013. We thank J. Vielmetter of the Caltech Protein Expression Facility for providing Fbxw7-Skp1, b-TrCP-Skp1, and ubiquitin E1. We thank B. Schulman, L. Busino, M. Pagano, F. Bassermann, O. Schneewind, A. Saha, and W. den Besten for gifts of reagents. We thank G. Smith for assistance with mass spectrometry analyses. We thank all the members of the Deshaies and Shan lab for support and helpful discussions. We thank D. Wolf and T. Kurz for communicating unpublished results. N.W.P. was supported by the Gordon Ross Fellowship, and an NIH Training Grant. J.E.L. was supported by the Ruth L. Kirschstein NRSA Fellowship (CA138126) from the NIH. R.J.D. is an Investigator of the HHMI. This work was supported in part by NIH GM065997 to R.J.D. The Proteome Exploration lab is supported in part by grants from the Gordon and Betty Moore Foundation and the Beckman Institute and an instrumentation grant from NIH (10565784).
Funding AgencyGrant Number
Gordon Ross FellowshipUNSPECIFIED
NIH Predoctoral FellowshipCA138126
Gordon and Betty Moore FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC3656483
Record Number:CaltechAUTHORS:20130517-081333288
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Official Citation: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, Cand1 Promotes Assembly of New SCF Complexes through Dynamic Exchange of F Box Proteins, Cell, Volume 153, Issue 1, 28 March 2013, Pages 206-215, ISSN 0092-8674, 10.1016/j.cell.2013.02.024. (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:38552
Deposited By: Ruth Sustaita
Deposited On:28 May 2013 23:30
Last Modified:09 Nov 2021 23:38

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