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The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions.

Publication ,  Journal Article
Harvey, CB; Bassett, JHD; Maruvada, P; Yen, PM; Williams, GR
Published in: Endocrinology
April 2007

The THRB gene encodes the well-described thyroid hormone (T3) receptor (TR) isoforms TRbeta1 and TRbeta2 and two additional variants, TRbeta3 and TRDeltabeta3, of unknown physiological significance. TRbeta1, TRbeta2, and TRbeta3 are bona fide T3 receptors that bind DNA and T3 and regulate expression of T3-responsive target genes. TRDeltabeta3 retains T3 binding activity but lacks a DNA binding domain and does not activate target gene transcription. TRDeltabeta3 can be translated from a specific TRDeltabeta3 mRNA or is coexpressed with TRbeta3 from a single transcript that contains an internal TRDeltabeta3 translation start site. In these studies, we provide evidence that the TRbeta3/Deltabeta3 locus is present in rat but not in other vertebrates, including humans. We compared the activity of TRbeta3 with other TR isoforms and investigated mechanisms of action of TRDeltabeta3 at specific thyroid hormone response elements (TREs) in two cell types. TRbeta3 was the most potent isoform, but TR potency was TRE dependent. TRDeltabeta3 acted as a cell-specific and TRE-dependent modulator of TRbeta3 when coexpressed at low concentrations. At higher concentrations, TRDeltabeta3 was a TRE-selective and cell-specific antagonist of TRalpha1, -beta1, and -beta3. Both TRbeta3 and TRDeltabeta3 were expressed in the nucleus in the absence and presence of hormone, and their actions were determined by cell type and TRE structure, whereas TRDeltabeta3 actions were also dependent on the TR isoform with which it interacted. Analysis of these complex responses implicates a range of nuclear corepressors and coactivators as cell-, TR isoform-, and TRE-specific modulators of T3 action.

Duke Scholars

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

April 2007

Volume

148

Issue

4

Start / End Page

1764 / 1773

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Thyroid Hormone Receptors beta
  • Species Specificity
  • Sequence Homology, Nucleic Acid
  • Response Elements
  • Rats
  • Protein Isoforms
  • Organ Specificity
  • Molecular Sequence Data
 

Citation

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Harvey, C. B., Bassett, J. H. D., Maruvada, P., Yen, P. M., & Williams, G. R. (2007). The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions. Endocrinology, 148(4), 1764–1773. https://doi.org/10.1210/en.2006-1248
Harvey, Clare B., JH Duncan Bassett, Padma Maruvada, Paul M. Yen, and Graham R. Williams. “The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions.Endocrinology 148, no. 4 (April 2007): 1764–73. https://doi.org/10.1210/en.2006-1248.
Harvey CB, Bassett JHD, Maruvada P, Yen PM, Williams GR. The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions. Endocrinology. 2007 Apr;148(4):1764–73.
Harvey, Clare B., et al. “The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions.Endocrinology, vol. 148, no. 4, Apr. 2007, pp. 1764–73. Pubmed, doi:10.1210/en.2006-1248.
Harvey CB, Bassett JHD, Maruvada P, Yen PM, Williams GR. The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions. Endocrinology. 2007 Apr;148(4):1764–1773.
Journal cover image

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

April 2007

Volume

148

Issue

4

Start / End Page

1764 / 1773

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Thyroid Hormone Receptors beta
  • Species Specificity
  • Sequence Homology, Nucleic Acid
  • Response Elements
  • Rats
  • Protein Isoforms
  • Organ Specificity
  • Molecular Sequence Data