Cullin 5-RING E3 ubiquitin ligases, new therapeutic targets?

Ubiquitylation is a reversible post-translational modification of proteins that controls a myriad of functions and cellular processes. It occurs through the sequential action of three distinct enzymes. E3 ubiquitin ligases (E3s) play the role of conductors of the ubiquitylation pathway making them attractive therapeutic targets. This review is dedicated to the largest family of multimeric E3s, the Cullin-RING E3 (CRL) family and more specifically to cullin 5 based CRLs that remains poorly characterized. •CRLs are key players of the ubiquitylation pathway.•CRL activity is highly regulated.•CRL5s targeted specific protein substrates to degradation by the proteasome.•CRLs that belong to the largest family of E3s represent promising drug targets.