Differential effects of retinoic acid isomers on the expression of nuclear receptor co-regulators in neuroblastoma

Penny E. Lovat, Margherita Annicchiarico-Petruzzelli, Marco Corazzari, Mark G. Dobson, Archie J. Malcolm, Andy D J Pearson, Gerry Melino, Christopher P F Redfern

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)415-419
Number of pages5
JournalFEBS Letters
Issue number2-3
Publication statusPublished - Feb 26 1999


  • 9-cis retinoic acid
  • All-trans retinoic acid
  • Co-activator
  • Co-repressor
  • Neuroblastoma
  • SMRT
  • TIF1
  • Trip3

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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