Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published November 30, 2017 | Supplemental Material + Accepted Version
Journal Article Open

Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases


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.

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.

Attached Files

Accepted Version - nihms913228.pdf

Supplemental Material - mmc1.xlsx

Supplemental Material - mmc2.xlsx


Files (2.8 MB)
Name Size Download all
148.4 kB Download
70.7 kB Download
2.6 MB Preview Download

Additional details

August 21, 2023
October 17, 2023