Separation of Transactivation and AP1 Antagonism Functions of Retinoic Acid Receptor (*)

Retinoic acid receptors (RARs) regulate gene expression either by directly binding to the RAR-responsive elements or by antagonizing the action of c-Jun/c-Fos (AP1). AP1 is involved in the expression of metalloproteases, cytokines and other factors which play critical roles in the turnover of extracellular matrix, inflammation and hyperproliferation in diseases such as psoriasis, rheumatoid arthritis and in tumor metastases. We demonstrate here that synthetic retinoids inhibit 12-O-tetradecanoylphorbol-14-acetate-induced transcription from the stromelysin AP1 motif through RARα, -β, and -. Interestingly, these diaryl acetylenic retinoids, which are potent agonists only for RARβ and RAR, but not for RARα, in transactivation assays, are able to inhibit AP1-dependent gene expression through RARα. Thus these analogs can differentially affect the transactivation and AP1 antagonistic functions of RARα. These results demonstrate that the transactivation and AP1 antagonistic functions are separable, and it should be possible to develop retinoids that are completely specific for AP1 antagonism through all RARs. Furthermore, using an RAR-selective ligand, we also demonstrate the separation of ligand binding and AP1 antagonism functions of RARs.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-01-13

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.270.2.923PMID 7822331
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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