Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity

Journal Article

Retinoid receptors are ligand activated transcription factors that regulate gene transcription through a complex network of interactions with members of the nuclear hormone receptor superfamily. Although ligand is required for trans-activation, addition of ligand to mammalian cells in vitro complicates the study of individual activated retinoid receptors. In order to circumvent this problem we have constructed a series of retinoid receptors which do not require ligand for trans-activation. This was accomplished by fusing the acidic activation domain of the herpes simplex viral protein VP16 to the carboxyl terminus of individual retinoid receptors. All of the chimeric receptors were found to exhibit constitutive trans-activation activity in CV-1 and P19 cells when cotransfected with a reporter that contained a trimerized retinoic acid receptor-β2 (RARβ2) retinoic acid response element. Further analysis conducted on reporters containing either the RARβ2 promoter or the rat cellular retinol binding protein II (rCRBPII) promoter showed that promoter specificity was well conserved between the chimeric receptors in the absence of exogenous retinoid and their ligand- induced native counterparts. Moreover, on the RARβ2 promoter reporter construct, the chimeric retinoid receptors displayed both cell type and inter- and intrafamily differences in trans-activation, whereas, trans- activation of the rCRBPII in the absence of exogenous ligand in CV-1 and P19 cells was found to be stimulated only by chimeric retinoid X receptor-α (RXRα). In P19 cells trans-activation of the rCRBPII promoter by RXRαv in the absence of exogenous ligand was inhibited by RARα and the constitutive forms of RARα, RARβ, RARγ, RXRβ, and to a lesser extent RXRγ.

Full Text

Duke Authors

Cited Authors

  • Underhill, TM; Cash, DE; Linney, E

Published Date

  • 1994

Published In

  • Molecular Endocrinology

Volume / Issue

  • 8 / 3

Start / End Page

  • 274 - 285

Digital Object Identifier (DOI)

  • 10.1210/me.8.3.274