INVESTIGATION ON THE POTENTIAL ROLE OF THE AH RECEPTOR NUCLEAR TRANSLOCATOR PROTEIN IN VITAMIN-D RECEPTOR ACTION

The Ah receptor nuclear translocator protein (ARNT) is required for bi nding of the Ah (dioxin) receptor to the xenobiotic responsive element (XRE), and is a structural component of the XRE-binding form of the A h receptor. The vitamin D receptor requires an accessory protein for b inding to the vitamin D responsive element (VDRE) in the osteocalcin g ene. Since the vitamin D receptor has similarities to the Ah receptor, we investigated whether ARNT is also required for vitamin D receptor activity. Two lines of evidence demonstrate that ARNT is not required for vitamin D receptor activity, and therefore does not correspond to the vitamin D receptor accessory protein: i) Antibodies to ARNT have n o effect on binding of the vitamin D receptor to the VDRE. ii) c4, a m utant of Hepa-1 cells that is defective in ARNT activity, and in which binding of the Ah receptor to the XRE does not occur, possesses a vit amin D receptor with full activity for binding the VDRE.