Sumo‐modification of pxr alters protein cofactor interactions (1062.11)

Abstract

Pregnane X Receptor (PXR, NR1I2) is a ligand‐activated nuclear receptor superfamily member expressed at high levels within the entero‐hepatic system in mammals. The primary function of PXR is to regulate the metabolism and transport of xenobiotics and endogenous compounds by controlling the expression of genes encoding major drug metabolizing enzymes and drug transporter proteins. To mediate its function PXR interacts with a plethora of classical co‐regulatory proteins including, but not limited to, Nuclear Receptor Co‐Repressors (NCoR1/NCoR2), Steroid Receptor Co‐activator proteins (SRC‐1/SRC‐2/SRC‐3) and p300/CBP co‐integrator proteins. SUMOylation is a reversible post‐translational modification that plays a central role in regulating multiple cellular activities such as protein‐protein interactions. While direct PXR‐target gene activation programs are currently well characterized, little is known about SUMO‐modification of PXR. Our working hypothesis is that SUMO‐modified PXR alters its protein‐protein interaction profile. Thus, we have created a GAL4‐PXR fusion system that allows us to directly examine SUMO‐PXR interaction with the aforementioned PXR‐binding proteins. Future efforts are focused on developing novel methods for identification of SUMO‐PXR‐binding proteins using non‐biased methods.Grant Funding Source: Supported by NIH DK090558