INTERACTION OF THE PEROXISOME-PROLIFERATOR-ACTIVATED RECEPTOR AND RETINOID X-RECEPTOR

The rat peroxisome-proliferator-activated receptor (PPAR) was expressed in insect cells and was shown to bind to a cognate PPAR response element (PPRE) from the acyl-CoA oxidase gene. Upon purification, PPAR was no longer able to bind DNA, although binding could be restored by addition of insect cell extracts. We investigated whether the retinoid X receptor (RXR) could supplement for this accessory activity. The rat RXRalpha cDNA was cloned and it was found that addition of in vitro-translated RXRalpha to purified PPAR facilitated binding of PPAR to a PPRE. Furthermore, an additional activity, which appeared to be distinct from rRXRalpha, was found in COS cell nuclear extracts that enabled binding of PPAR to a PPRE. Transient expression of RXRalpha in CHO cells was found to be essential for the response of a chloramphenicol acetyltransferase reporter construct containing PPREs to activators of PPAR. These results raise the possibility of convergence of the PPAR and retinoid-dependent signaling pathways on promoters containing PPRE-like responsive elements.