Trade-off and flexibility in the dynamic regulation of the cullin-RING ubiquitin ligase repertoire.

ABSTRACT: Cullin-RING ubiquitin ligases (CRLs) catalyze the ubiquitylation of substrates many of which are degraded by the 26S proteasome. Their modular architecture enables recognition of numerous substrates via exchangeable substrate receptors that competitively bind to a cullin scaffold with high affinity. Due to the plasticity of these interactions there is ongoing uncertainty how cells maintain a flexible CRL repertoire in view of changing substrate loads. Based on a series of in vivo and in vitro studies, different groups proposed that the exchange of substrate receptors is mediated by a protein exchange factor named Cand1. Here, we have performed mathematical modeling to provide a quantitative underpinning of this hypothesis. First we show that the exchange activity of Cand1 necessarily leads

SUBMITTER: Straube R 

PROVIDER: S-EPMC5711038 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature