Ubiquitylation of nuclear receptors: new linkages and therapeutic implications

The nuclear receptor (NR) superfamily is a group of transcriptional regulators that control multiple aspects of both physiology and pathology and are broadly recognized as viable therapeutic targets. While receptor-modulating drugs have been successful in many cases, the discovery of new drug targets is still an active area of research, because resistance to NR-targeting therapies remains a significant clinical challenge. Many successful targeted therapies have harnessed the control of receptor activity by targeting events within the NR signaling pathway. In this review, we explore the role of NR ubiquitylation and discuss how the expanding roles of ubiquitin could be leveraged to identify additional entry points to control receptor function for future therapeutic development.