Pregnane and Xenobiotic Receptor (PXR/SXR) resides predominantly in the nuclear compartment of the interphase cell and associates with the condensed chromosomes during mitosis

Abstract

Pregnane and Xenobiotic Receptor (PXR) is a transcription factor that is activated by a diverse range of xenobiotics and endogenous metabolites including steroids, bile acids and about 50% of the prescription drugs. In specific cell types (e.g. liver and intestine) it serves as a 'xenosensor' by regulating expression of a network of genes involved in xenobiotic clearance from the body. PXR expression in several cancerous tissues and its regulated expression of multi-drug resistance proteins highlight its significance in prognosis of malignancies. The view that subcellular localization and ligand induced movements of transcription factors is one of the major phenomena in regulating transcriptional activity, we used a green fluorescent protein tagged PXR chimera to study its dynamic behaviour in living cells. Under all experimental conditions, PXR was observed to be a predominantly nuclear protein maintaining a dynamic equilibrium between the nuclear and cytoplasmic compartments of the interphase cells. Interestingly, for the first time, a member of the nuclear receptor superfamily, PXR, has been observed to be associated with condensed chromosomes during all the mitotic stages of cell division. The significance of PXR association with mitotic chromosomes is discussed.