Interaction of the peroxisome-proliferator-activated receptor and retinoid X receptor

K. L. Gearing, M. Gottlicher, M. Teboul, E. Widmark, J. A. Gustafsson

Research output: Contribution to journalArticlepeer-review

348 Scopus citations

Abstract

The rat peroxisome-proliferator-activated receptor (PPAR) was expressed in insect cells and was shown to bind to a cognate PPAR response element (PPRE) from the acyl-CoA oxidase gene. Upon purification, PPAR was no longer able to bind ONA, although binding could be restored by addition of insect cell extracts. We investigated whether the retinoid X receptor (RXR) could supplement for this accessory activity. The rat RXRa cDNA was cloned and it was found that addition of in vitro-translated RXRa to purified PPAR facilitated binding of PPAR to a PPRE. Furthermore, an additional activity, which appeared to be distinct from rRXRα, was found in COS cell nuclear extracts that enabled binding of PPAR to a PPRE. Transient expression of RXRα in CHO cells was found to be essential for the response of a chloramphenicol acetyltransferase reporter construct containing PPREs to activators of PPAR. These results raise the possibility of convergence of the PPAR and retinoid-dependent signaling pathways on promoters containing PPRE-like responsive elements.

Original languageEnglish (US)
Pages (from-to)1440-1444
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number4
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • General

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