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Lookup NU author(s): Professor Penny Lovat,
Dr Mark Dobson,
Professor Archibald Malcolm,
Professor Andrew Pearson,
Dr Chris Redfern
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Retinoic acid modulates growth and induces differentiation and apoptosis of neuroblastoma cells in vitro, with the all-trans and 9-cis isomers having different biological properties. Transcriptional activation in response to retinoic acid isomers is mediated by retinoic acid receptors and retinoid X receptors. The differential expression of co-activators and co-repressors which preferentially interact with retinoic acid receptors or retinoid X receptors may be a mechanism leading to different cellular responses to 9-cis and all-trans retinoic acid. To test this hypothesis, we have studied the expression of the nuclear receptor co-regulators TIF1α, TIF1β, SUG1 and SMRT in the N-type and S-type neuroblastoma cell lines SH SY 5Y and SH S EP. Transcripts for all four co-regulators were expressed in these neuroblastoma cells. The expression of TIF1α, TIF1β and SUG1 did not change in response to retinoic acid; however, SMRT was induced in both neuroblastoma cell lines, but particularly by all-trans retinoic acid in SH S EP cells. An additional co-activator, Trip3, was isolated by differential mRNA display and shown to be preferentially induced by 9-cis retinoic acid in SH SY 5Y and SH S EP cells. These data suggest that retinoic acid isomer-specific induction of nuclear receptor co-regulators may determine, in part, the differential biological effects of retinoic acid isomers. Copyright (C) 1999 Federation of European Biochemical Societies.
Author(s): Lovat, P.E., Annicchiarico-Petruzzelli, M., Corazzari, M., Dobson, M., Malcolm, A.J., Pearson, A.D.J., Melino, G., Redfern, C.P.F.
Publication type: Article
Publication status: Published
Journal: FEBS Letters
Print publication date: 26/02/1999
ISSN (print): 0014-5793
ISSN (electronic): 1873-3468
PubMed id: 10094499
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