Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

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.

Research highlights
► Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation.
► PXR undergoes dynamic deacetylation upon ligand-mediated activation.
► SIRT1 partially mediates PXR deacetylation.
► PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation.