Dataset Information


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 koff of an FBP from SCF by the actions of substrate, Nedd8, and Cand1 molds the cellular repertoire of SCF complexes and that the plasticity afforded by this exchange mechanism may enable large variations in FBP expression during development and in FBP gene number during evolution.


PROVIDER: S-EPMC5836512 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3656483 | BioStudies
1000-01-01 | S-EPMC2448860 | BioStudies
2017-01-01 | S-EPMC5711595 | BioStudies
1000-01-01 | S-EPMC3255936 | BioStudies
2013-01-01 | S-EPMC3637025 | BioStudies
2009-01-01 | S-EPMC2779159 | BioStudies
1000-01-01 | S-EPMC2586271 | BioStudies
2013-01-01 | S-EPMC3698631 | BioStudies
2019-01-01 | S-EPMC6739345 | BioStudies
1000-01-01 | S-EPMC3436198 | BioStudies