Novel Insights Into E3 Ubiquitin Ligase in Cancer Chemoresistance

Abstract

Drug resistance can obstruct successful cancer chemotherapy. The ubiquitin-proteasome pathway has emerged as a crucial player that controls steady-state protein levels regulating multiple biological processes, such as cell cycle, cellular proliferation, apoptosis, and DNA damage response, which are involved in oncogenesis, cancer development, prognosis, and drug resistance. E3 ligases perform the final step in the ubiquitination cascade, and determine which protein becomes ubiquitylated by specifically binding the substrate protein. They are promising drug targets thanks to their ability to regulate protein stability and functions. Although patient survival has increased in recent years with the availability of novel agents, chemoresistance remains a major problem in cancer management. E3 ligases attract increasing attention with advances in chemoresistance knowledge. To explore the role of E3 ligase in cancer chemotherapy resistance and the underlying mechanism, we summarize the growing number of E3 ligases and their substrate proteins, which have emerged as crucial players in cancer chemoresistance and targeted therapies.

Keywords: Chemoresistance; E3 ubiquitin ligases; Substrate protein; Target therapy; Ubiquitin-proteasome pathway.