Cand1-Mediated Adaptive Exchange Mechanism Enables Variation in F-Box Protein Expression.

ABSTRACT: Skp1⋅Cul1⋅F-box (SCF) ubiquitin ligase assembly is regulated by the interplay of substrate binding, reversible Nedd8 conjugation on Cul1, and the F-box protein (FBP) exchange factors Cand1 and Cand2. Detailed investigations into SCF assembly and function in reconstituted systems and Cand1/2 knockout cells informed the development of a mathematical model for how dynamical assembly of SCF complexes is controlled and how this cycle is coupled to degradation of an SCF substrate. Simulations predicted an unanticipated hypersensitivity of Cand1/2-deficient cells to FBP expression levels, which was experimentally validated. Together, these and prior observations lead us to propose the adaptive exchange hypothesis, which posits that regulation of the k_off of an FBP from SCF by the actio

SUBMITTER: Liu X 

PROVIDER: S-EPMC5836512 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature