Monoubiquitination of pro-amphiregulin regulates its endocytosis and ectodomain shedding

► Endogenous pro-AREG was monoubiquitinated in MCF7 cells. ► Lysine 240 of pro-AREG was the primary ubiquitin acceptor residue. ► Monoubiquitin-fused pro-AREG was rapidly endocytosed and localized to early endosomes. ► Monoubiquitin of pro-AREG down-regulate efficiency of ectodomain shedding.