Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma

In an effort to understand transcriptional regulation by the peroxisome pro liferator-activated receptor gamma (PPAR gamma), we have investigated its p otential interaction with coregulators and have identified ARA70 as a ligan d-enhanced coactivator. ARA70 was initially described as a coactivator for the androgen receptor (AR) and is expressed in a range of tissues including adipose tissue (Yeh, S., and Chang, C. (1996) Proc. Natl. Acad. Sci. U.S. A. 93, 5517-5521), Here we show that ARA70 and PPAR gamma specifically inte ract by coimmunoprecipitation and in a mammalian two-hybrid assay. PPAR gam ma and ARA70 interact in the absence of the PPAR gamma ligand 15-deoxy-Delt a 12,14-prostaglandin J2, although the addition of exogenous ligand enhance s this interaction. Similarly, in transient transfection of DU145 cells, co transfection of PPAR gamma and ARA70 induces transcription from re porter c onstructs driven by either three copies of an isolated PPAR response elemen t or the natural promoter of the adipocyte fatty acid-binding protein 2 in the absence of exogenous 15-deoxy-Delta 12,14-prostaglandin J2. However, th is PPAR gamma-ARA70 transactivation is enhanced by the addition of ligand. Thus, ARA70 can function as a ligand-enhanced coactivator of PPAR gamma. Fi nally, we show that AR can squelch PPAR gamma-ARA70 transactivation, which suggests that cross-talk may occur between PPAR gamma- and AR-mediated resp onses in adipocytes.