A CULLINary ride across the secretory pathway: more than just secretion

• Particular cullin-RING ubiquitin ligases (CRLs) are localized to the secretory pathway.
• At the ER, CRLs modify vesicle coat proteins and may aid large cargo export.
• CRLs aid ER-associated destruction of misfolded proteins.
• Unidentified CRL substrates regulate the maintenance of normal Golgi structure.
• CRLs may regulate secretory flux, cell cycle progression, and Wnt signaling.

Mulitmeric cullin-RING ubiquitin ligases (CRLs) represent the largest class of ubiquitin ligases in eukaryotes. However, most CRL ubiquitylation pathways remain uncharacterized. CRLs control a myriad of functions by catalyzing mono- or poly-ubiquitylation of target proteins. Recently, novel CRLs have been identified along the secretory pathway where they modify substrates involved in diverse cellular processes such as vesicle coat assembly and cell cycle progression. This review discusses our current understanding of CRL ubiquitylation within the secretory pathway, with special emphasis on the emerging role of the Golgi as a ubiquitylation platform. CRLs are also implicated in endosome function, where their specific roles are less well understood.