Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Nov 7

PMID 29103612

Citations 74

Authors

Justin M Reitsma

Xing Liu

Kurt M Reichermeier

Annie Moradian

Michael J Sweredoski

Sonja Hess

Raymond J Deshaies

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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C-terminal amides mark proteins for degradation via SCF-FBXO31.

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