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Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity.

Publication ,  Journal Article
Underhill, TM; Cash, DE; Linney, E
Published in: Mol Endocrinol
March 1994

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-beta 2 (RAR beta 2) retinoic acid response element. Further analysis conducted on reporters containing either the RAR beta 2 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 RAR beta 2 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-alpha (RXR alpha). In P19 cells trans-activation of the rCRBPII promoter by RXR alpha v in the absence of exogenous ligand was inhibited by RAR alpha and the constitutive forms of RAR alpha, RAR beta, RAR gamma, RXR beta, and to a lesser extent RXR gamma.

Duke Scholars

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

March 1994

Volume

8

Issue

3

Start / End Page

274 / 285

Location

United States

Related Subject Headings

  • Viral Fusion Proteins
  • Tumor Cells, Cultured
  • Transcriptional Activation
  • Transcription Factors
  • Simplexvirus
  • Retinol-Binding Proteins, Cellular
  • Retinol-Binding Proteins
  • Retinoid X Receptors
  • Receptors, Retinoic Acid
  • Receptors, Cytoplasmic and Nuclear
 

Citation

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Underhill, T. M., Cash, D. E., & Linney, E. (1994). Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity. Mol Endocrinol, 8(3), 274–285. https://doi.org/10.1210/mend.8.3.8015546
Underhill, T. M., D. E. Cash, and E. Linney. “Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity.Mol Endocrinol 8, no. 3 (March 1994): 274–85. https://doi.org/10.1210/mend.8.3.8015546.
Underhill TM, Cash DE, Linney E. Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity. Mol Endocrinol. 1994 Mar;8(3):274–85.
Underhill, T. M., et al. “Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity.Mol Endocrinol, vol. 8, no. 3, Mar. 1994, pp. 274–85. Pubmed, doi:10.1210/mend.8.3.8015546.
Underhill TM, Cash DE, Linney E. Constitutively active retinoid receptors exhibit interfamily and intrafamily promoter specificity. Mol Endocrinol. 1994 Mar;8(3):274–285.

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

March 1994

Volume

8

Issue

3

Start / End Page

274 / 285

Location

United States

Related Subject Headings

  • Viral Fusion Proteins
  • Tumor Cells, Cultured
  • Transcriptional Activation
  • Transcription Factors
  • Simplexvirus
  • Retinol-Binding Proteins, Cellular
  • Retinol-Binding Proteins
  • Retinoid X Receptors
  • Receptors, Retinoic Acid
  • Receptors, Cytoplasmic and Nuclear