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Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases

Reitsma, Justin M. and Liu, Xing and Reichermeier, Kurt M. and Moradian, Annie and Sweredoski, Michael J. and Hess, Sonja and Deshaies, Raymond J. (2017) Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases. Cell, 171 (6). pp. 1326-1339. ISSN 0092-8674. PMCID PMC5711595. doi:10.1016/j.cell.2017.10.016.

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SCF (Skp1-Cullin-F-box) ubiquitin ligases comprise several dozen modular enzymes that have diverse roles in biological regulation. SCF enzymes share a common catalytic core containing Cul1⋅Rbx1, which is directed toward different substrates by a variable substrate receptor (SR) module comprising 1 of 69 F-box proteins bound to Skp1. Despite the broad cellular impact of SCF enzymes, important questions remain about the architecture and regulation of the SCF repertoire, including whether SRs compete for Cul1 and, if so, how this competition is managed. Here, we devise methods that preserve the in vivo assemblages of SCF complexes and apply quantitative mass spectrometry to perform a census of these complexes (the “SCFome”) in various states. We show that Nedd8 conjugation and the SR exchange factor Cand1 have a profound effect on shaping the SCFome. Together, these factors enable rapid remodeling of SCF complexes to promote biased assembly of SR modules bound to substrate.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Liu, Xing0000-0002-0506-6821
Moradian, Annie0000-0002-0407-2031
Sweredoski, Michael J.0000-0003-0878-3831
Hess, Sonja0000-0002-5904-9816
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2017 Elsevier Inc. Received 14 March 2017, Revised 17 July 2017, Accepted 12 October 2017, Available online 2 November 2017, Published: November 2, 2017. We would like to thank Christina Ludwig and Ruedi Aebersold for providing J.M.R. with technical training in SRM mass spectrometry. We also thank Don Cleveland for reagents. Finally, we thank the Deshaies lab and the Proteome Exploration Laboratory for helpful discussions. M.J.S., A.M., and S.H. were supported by the Gordon and Betty Moore Foundation (GBMF775) and the Beckman Institute. J.M.R. is supported by F32 grant GM112308. X.L. is supported by the Jane Coffin Childs Memorial Fund for Medical Research (61-1516). R.J.D. is an Investigator of the Howard Hughes Medical Institute and this work was supported in part by HHMI. Author Contributions: Conceptualization, J.M.R. and R.J.D.; Experimentation, J.M.R., X.L., and K.M.R., Resources, J.M.R., X.L., K.M.R., A.M., and S.H.; Funding Acquisition and Supervision, J.M.R., X.L., S.H., and R.J.D.; Visualization and Writing, J.M.R., M.J.S., K.M.R., and R.J.D.
Funding AgencyGrant Number
Gordon and Betty Moore FoundationGBMF775
Caltech Beckman InstituteUNSPECIFIED
Jane Coffin Childs Memorial Fund for Medical Research61-1516
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:cullin-RING; CRL; proteasome; ubiquitin; E3 ligase; Cop9 signalosome; SRM; MRM
Issue or Number:6
PubMed Central ID:PMC5711595
Record Number:CaltechAUTHORS:20171102-102235105
Persistent URL:
Official Citation:Justin M. Reitsma, Xing Liu, Kurt M. Reichermeier, Annie Moradian, Michael J. Sweredoski, Sonja Hess, Raymond J. Deshaies, Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases, In Cell, Volume 171, Issue 6, 2017, Pages 1326-1339.e14, ISSN 0092-8674,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:82886
Deposited By: Tony Diaz
Deposited On:02 Nov 2017 17:34
Last Modified:21 Mar 2022 17:16

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