Phosphorylation of nuclear receptors: Novelty and therapeutic implications

Nuclear receptors (NR) collectively regulate several biological functions in various organs. While NRs can be characterized by activation of the transcription of their signature genes, they also have other diverse roles. Although most NRs are directly activated by ligand binding, which induces cascades of events leading to gene transcription, some NRs are also phosphorylated. Despite extensive investigations, primarily focusing on unique phosphorylation of amino acid residues in different NRs, the role of phosphorylation in the biological activity of NRs in vivo has not been firmly established. Recent studies on the phosphorylation of conserved phosphorylation motifs within the DNA-and ligand-binding domains confirmed has indicated the physiologically relevance of NR phosphorylation. This review focuses on estrogen and androgen receptors, and highlights the concept of phosphorylation as a drug target. Published by Elsevier Inc.

Automated summary

Nuclear receptors collectively regulate biological functions and have diverse roles beyond transcription activation. While most are activated by ligand binding, some are phosphorylated. The physiological relevance of phosphorylation in nuclear receptor activity has been confirmed, especially within conserved domains. This review focuses on estrogen and androgen receptors and highlights phosphorylation as a potential drug target.