Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases.
Cell
; 171(6): 1326-1339.e14, 2017 Nov 30.
Article
in En
| MEDLINE
| ID: mdl-29103612
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 Cul1â
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
SKP Cullin F-Box Protein Ligases
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2017
Type:
Article
Affiliation country:
United States