E3 ubiquitin ligases in cancer and implications for therapies

E3 ligases are a class of enzymes that can transfer ubiquitin to substrates for their degradation, which are of importance in cellular homeostasis. Since many oncogenic or tumor-suppressive proteins are reported to be regulated by the ubiquitin-proteasome system (UPS), E3 ligases, which function as substrate interacting modules, have been attracting more and more attention as promising anticancer drug targets due to their pivotal role in conferring substrate specificity. Generally, based on their molecular structure and functional mechanism, E3 ligases can be divided into three major types: homologous to E6-associated protein C-terminus (HECT), really interesting new gene (RING), and RING-in-between-RING (RBR) E3 ligases. Based on the significance of their functions, more bioactive compounds targeting E3 ligases should be developed in the future. In this review, we discuss the important roles of E3 ligases involved in cancer as well as available bioactive compounds targeting various E3 ligases for potential anticancer activity.