Regulated ubiquitination and SUMOylation of pregnane X receptor (1062.10)

Highly expressed in the entero‐hepatic system, pregnane X receptor (PXR, NR1I2) is a well‐characterized nuclear receptor that regulates the expression of genes encoding key drug metabolizing enzymes and drug transporter proteins. The net effect of PXR activation is to increase metabolism and clearance of drugs and xenobiotics from the body. Activation of PXR also plays a pivotal role in mediating adverse drug‐drug interactions. The complete understanding of PXR biology is thus important for the prevention of adverse drug‐drug interactions and the development of safe and effective therapeutic strategies. Recent research recognizes that post‐translational modification (PTM) of PXR (e.g; phosphorylation, ubiquitination, SUMOylation) significantly impacts its function; however, these studies are still in their infancy. Here we present a novel method of determining the extent to which ubiquitination and SUMOylation of PXR occurs. Our data indicate that PXR is the simultaneous target of the ubiquitin and SUMO signaling pathways, and that these PTMs modulate PXR‐biological activity. Grant Funding Source : Supported by NIH‐090558