Reference - PMID:23535663 - CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire.
Reference summary
- PubMed ID
- PMID:23535663
- Title
- CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire.
- Authors
- Wu S, Zhu W, Nhan T, Toth JI, Petroski MD, Wolf DA
- Citation
- Nat Commun 2013;4:1642
- Publication year
- 2013
- Abstract
- The combinatorial architecture of cullin 1-RING ubiquitin ligases, in which multiple F-box containing substrate receptors compete for access to CUL1, poses special challenges to assembling cullin 1-RING ubiquitin ligase complexes through high affinity protein interactions while maintaining the flexibility to dynamically sample the entire F-box containing substrate receptor repertoire. Here, using highly quantitative mass spectrometry, we demonstrate that this problem is addressed by CAND1, a factor that controls the dynamics of the global cullin 1-RING ubiquitin ligase network by promoting the assembly of newly synthesized F-box containing substrate receptors with CUL1-RBX1 core complexes. Our studies of in vivo cullin 1-RING ubiquitin ligase dynamics and in vitro biochemical findings showing that CAND1 can displace F-box containing substrate receptors from Cul1p suggest that CAND1 functions in a cycle that serves to exchange F-box containing substrate receptors on CUL1 cores. We propose that this cycle assures comprehensive sampling of the entire F-box containing substrate receptor repertoire in order to maintain the cullin 1-RING ubiquitin ligase landscape, a function that we show to be critical for substrate degradation and normal physiology.
