title: Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization.
abstract: Cullin-RING E3 ubiquitin-Ligases (CRLs) are the most prominent class of ubiquitin-ligases. By controlling the stability of a cohort of key regulators, CRLs impinge on many cellular and biological processes such as immunity, development, transcription, cell signalling and cell cycle progression. CRLs are multi-subunit complexes composed of a catalytic site and a substrate recognition module nucleated around a cullin scaffold protein. Most eukaryotic genomes encode at least five distinct cullins, and each of these cullins recruits a specific substrate-recognition module such that CRL complexes are modular. Despite their considerable diversity, CRLs are regulated by similar mechanisms. In particular, recent observations indicate that conformational variability induced by CRL dimerization and by conjugation of the ubiquitin-like protein NEDD8 on the cullin subunit stimulates substrate polyubiquitination. In this review, we discuss the composition of CRL complexes and the various molecular mechanisms controlling their activity.
authors.affiliation: Institut Jacques Monod, CNRS, Université Paris Diderot et UPMC, 2 place Jussieu Tour 43, 75251, Paris Cedex 05, France.
authors.forename: J
authors.initials: J
authors.lastname: Merlet
authors.forename: J
authors.initials: J
authors.lastname: Burger
authors.forename: J-E
authors.initials: JE
authors.lastname: Gomes
authors.forename: L
authors.initials: L
authors.lastname: Pintard
mesh_terms: D000818:Animals; D029681:Arabidopsis Proteins / Q000378:metabolism; D044842:Cullin Proteins / Q000737:chemistry / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004789:Enzyme Activation; D000075687:NEDD8 Protein; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013379:Substrate Specificity; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D044842:Cullin Proteins; D029721:Drosophila Proteins; D000075687:NEDD8 Protein; C513173:Nedd8 protein, Drosophila; C513170:RUB1 protein, Arabidopsis; C111706:RUB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins