title: CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire.
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.
authors.affiliation: Signal Transduction Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors.forename: Shuangding
authors.initials: S
authors.lastname: Wu
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhu
authors.forename: Tina
authors.initials: T
authors.lastname: Nhan
authors.forename: Julia I
authors.initials: JI
authors.lastname: Toth
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Petroski
authors.forename: Dieter A
authors.initials: DA
authors.lastname: Wolf
mesh_terms: D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D044843:SKP Cullin F-Box Protein Ligases
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