title: Acetylation of pregnane X receptor protein determines selective function independent of ligand activation.
abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.
authors.affiliation: Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Arunima
authors.initials: A
authors.lastname: Biswas
authors.forename: Danielle
authors.initials: D
authors.lastname: Pasquel
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Tyagi
authors.forename: Sridhar
authors.initials: S
authors.lastname: Mani
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D022781:Hepatocytes; D006801:Humans; D008024:Ligands; D050155:Lipogenesis; D051379:Mice; D018345:Mice, Knockout; D000077297:Pregnane X Receptor; D011499:Protein Processing, Post-Translational; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D008024:Ligands; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C447939:SIRT1 protein, human; D056564:Sirtuin 1