Integrities of A/B and C domains of RXR are required for rexinoid-induced caspase activations and apoptosis

Research output: Contribution to journalArticle


  • S Qin
  • Y Okawa
  • L Atangan
  • R Chandraratna

Colleges, School and Institutes


Here we have delineated regions of the retinoid X receptor alpha (RXRalpha) that are required for rexinoid (RXR agonist)-induced growth inhibition and apoptosis. Stable over-expression of RXRalpha in DT40 B lymphoma cells dramatically increased sensitivity to rexinoid-induced growth inhibition. By contrast, DT40 cells that over-expressed RXRalpha with a deletion of either the A/B or DNA binding domain (C domain) were resistant. We confirmed the importance of C domain integrity by point-mutating Cys(135) to Ser (C135S) to disrupt zinc-finger formation. Point mutating RXR Lys(201) to Thr and Arg(202) to Ala (KTRA) impairs RXR homodimer formation and does not affect RXR heterodimerization. When these mutated RXRs were over-expressed in DT40 cells, they failed to increase sensitivity to rexinoid. Over-expression did sensitize to growth inhibition by RAR and PPARgamma agonists. Over-expression of C135S mutated RXRalpha did not sensitize to RAR and PPARgamma agonists. Inhibitors of caspase-3 and/or caspase-9 blocked rexinoid-induced apoptosis, and activations of these caspases correlated with the ability of RXR mutants to induce cell death. These data show that the A/B and C domains of RXR and the ability of RXR to form homodimers are required for rexinoid-driven growth inhibition, caspase activation and subsequent apoptosis.


Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Issue number1-3
Publication statusPublished - 1 Nov 2008


  • Rexinoid, Homodimer, Apoptosis, Caspase, Retinoid X receptor, Growth inhibition