, Volume 21, Issue 2, pp 139-146

Induction and repression of peroxisome proliferator-activated receptor α transcription by coregulator ARA70

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In an effort to understand transcriptional regulation by the peroxisome proliferator-activated receptor α (PPARα), we investigated the ability of a number of transcriptional coactivators to enhance PPARα:retinoic acid receptor (RXR) mediated transcription. We identified ARA70, a coactivator of the androgen receptor and PPARγ, as a ligand-enhanced coactivator of PPARα in the prostate cancer cell line DU145. In prostate cancer cells, ARA70 demonstrated the strongest enhancement of PPARα transcription among the coactivators examined. Mutation of the N-terminal of the PPARα ligandbinding domain dramatically reduced the ability of ARA70 to enhance PPARα:RXR transcription. ARA70 was able to physically interact with both the wild-type and mutant PPARα as determined by coimmunoprecipitation. However, in the adrenal cell line Y1, ARA70 behaved as a repressor of PPARα while still able to coactivate PPARγ.