Acetylation of nuclear receptors in health and disease: an update.
Anthony W AshtonHarpreet K DhanjalBenjamin RossnerHuma MahmoodVivek I PatelMohammad NadimManpreet LotaFarhan ShahidZhiping LiDavid JoyceMatyas PajkosZsuzsanna DosztányiXuanmao JiaoRichard G PestellPublished in: The FEBS journal (2022)
Lysine acetylation is a common reversible post-translational modification of proteins that plays a key role in regulating gene expression. Nuclear receptors (NRs) include ligand-inducible transcription factors and orphan receptors for which the ligand is undetermined, which together regulate the expression of genes involved in development, metabolism, homeostasis, reproduction, and human diseases including cancer. Since the original finding that the ERα, AR, and HNF4 are acetylated, we now understand that the vast majority of NRs are acetylated and that this modification has profound effects on NR function. Acetylation sites are often conserved and involve both ordered and disordered regions of NRs. The acetylated residues function as part of an intramolecular signaling platform intersecting phosphorylation, methylation and other modifications. Acetylation of NR has been shown to impact recruitment into chromatin, co-repressor and coactivator complex formation, sensitivity and specificity of regulation by ligand and ligand antagonists, DNA binding, subcellular distribution and transcriptional activity. A growing body of evidence in mice indicates a vital role for NR acetylation in metabolism. Additionaly, mutations of the NR acetylation site occur in human disease. This review focuses on the role of NR acetylation in coordinating signaling in normal physiology and disease.
Keyphrases
- transcription factor
- gene expression
- histone deacetylase
- dna binding
- endothelial cells
- dna methylation
- poor prognosis
- public health
- healthcare
- induced pluripotent stem cells
- mental health
- squamous cell carcinoma
- genome wide
- oxidative stress
- dna damage
- autism spectrum disorder
- young adults
- toll like receptor
- papillary thyroid
- social media
- pluripotent stem cells
- health information
- insulin resistance
- long non coding rna
- quantum dots