Quantitative analyses for effects of neddylation on CRL2^VHL substrate ubiquitination and degradation.

ABSTRACT: Through catalyzing the ubiquitination of key regulatory proteins, cullin-RING ubiquitin ligases (CRLs) play essential biological roles and their activities are controlled by multiple mechanisms including neddylation, the conjugation of NEDD8 to cullins. Upon neddylation, a CRL, such as the CUL1-based CRL1, undergoes conformational changes that accelerate substrate ubiquitination. Given the structural diversity across subfamilies of CRLs and their substrates, to what extent neddylation modulates the activity of individual CRLs remains to be evaluated. Here, through reconstituting the CRL2 ubiquitination reaction in vitro, we showed that neddylation promotes CRL2^VHL -dependent degradation of both full-length HIF1α and the degron peptide of HIF1α, resulting in more than 10-fold inc

SUBMITTER: Wang K 

PROVIDER: S-EPMC8521307 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature