Induction and repression of peroxisome proliferator-activated receptor alpha transcription by coregulator ARA70.
In an effort to understand transcriptional regulation by the peroxisome proliferator-activated receptor alpha (PPARalpha), we investigated the ability of a number of transcriptional coactivators to enhance PPARalpha:retinoic acid receptor (RXR) mediated transcription. We identified ARA70, a coactivator of the androgen receptor and PPARgamma, as a ligand-enhanced coactivator of PPARalpha in the prostate cancer cell line DU145. In prostate cancer cells, ARA70 demonstrated the strongest enhancement of PPARalpha transcription among the coactivators examined. Mutation of the N-terminal of the PPARalpha ligandbinding domain dramatically reduced the ability of ARA70 to enhance PPARalpha:RXR transcription. ARA70 was able to physically interact with both the wild-type and mutant PPARalpha as determined by coimmunoprecipitation. However, in the adrenal cell line Y1, ARA70 behaved as a repressor of PPARalpha while still able to coactivate PPARgamma.
Heinlein
Cynthia A
CA
George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Chang
Chawnshang
C
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D015534:Trans-Activators; D014157:Transcription Factors