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      Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors.

      1 , , , ,
      Cell
      Elsevier BV

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          Abstract

          Transcriptional activation of the nuclear receptor RAR by retinoic acid (RA) often leads to inhibition of cell growth. However, in some tissues, RA promotes cell survival and hyperplasia, activities that are unlikely to be mediated by RAR. Here, we show that, in addition to functioning through RAR, RA activates the "orphan" nuclear receptor PPARbeta/delta, which, in turn, induces the expression of prosurvival genes. Partitioning of RA between the two receptors is regulated by the intracellular lipid binding proteins CRABP-II and FABP5. These proteins specifically deliver RA from the cytosol to nuclear RAR and PPARbeta/delta, respectively, thereby selectively enhancing the transcriptional activity of their cognate receptors. Consequently, RA functions through RAR and is a proapoptotic agent in cells with high CRABP-II/FABP5 ratio, but it signals through PPARbeta/delta and promotes survival in cells that highly express FABP5. Opposing effects of RA on cell growth thus emanate from alternate activation of two different nuclear receptors.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          0092-8674
          0092-8674
          May 18 2007
          : 129
          : 4
          Affiliations
          [1 ] Division of Nutritional Sciences, Cornell University, Ithaca, NY 14850, USA.
          Article
          S0092-8674(07)00449-7 NIHMS23938
          10.1016/j.cell.2007.02.050
          1948722
          17512406
          b14f8900-2e1c-429b-b0c3-0e35a0f7b8e3
          History

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