A NOVEL HETERODIMERIZATION PARTNER FOR THYROID-HORMONE RECEPTOR - PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR

Retinoid-like receptors play a central role in hormonal responses by f orming heterodimers with other nuclear hormone receptors. In this stud y we have identified the peroxisome proliferator-activated receptor (P PAR) as a new thyroid hormone receptor (THR) auxiliary nuclear protein , heterodimerizing with THR in solution. Although these heterodimers d o not recognize a classical thyroid hormone response element (TRE) cha racterized by direct repeat separated by four nucleotides (DR + 4), PP AR behaves as a dominant negative regulator of thyroid hormone (TH) ac tion. However a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodime r with a novel TRE (DR + 2). The critical region of THR beta was mappe d to 3 amino acids in the distal box of the DNA binding domain. Hence, PPAR can positively or negatively influence TH action depending on TR E structure and THR isotype.