Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors.
By T. Schug, Daniel C. Berry, N. Shaw, Skylar N. Travis, N. Noy. Cell, 2007
688 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0224e96bab9a5de69fd0982a448ca00efa565513
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In Molecular Biology
Citations in the corpus
- Vitamin effects on the immune system: vitamins A and D take centre stage (2008, background): “Notably, retinoic acid can also bind and signal through the PPARβ (also known as PPARδ) nuclear recepto”
- A global perspective on carotenoids: Metabolism, biotechnology, and benefits for nutrition and health. (2018, background): “The intracellular RA binding proteins CRABP-II and FABP5 are thought to deliver atRA to RARs and PPARβ/δ, respectively [440].”