nti glucocorticoid receptor transcripts lack sequences encoding the amino-terminal transcriptional modulatory domain

Ellen S. Dieken, Eckart U. Meese, Roger Miesfeld

Research output: Contribution to journalArticle

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Abstract

Glucocorticoid induction of cell death (apoptosis) in mouse lymphoma S49 cells has long been studied as a molecular genetic model of steroid hormone action. To better understand the transcriptional control of glucocorticoid-induced S49 cell death, we isolated and characterized glucocorticoid receptor (GR) cDNA from two steroid-resistant nti S49 mutant cell lines (S49.55R and S49.143R) and the wild-type parental line (S49.A2). Our data reveal that nti GR transcripts encode intact steroid- and DNA-binding domains but lack 404 amino-terminal residues as a result of aberrant RNA splicing between exons 1 and 3. Results from transient cotransfection experiments into CV1 cells using nti receptor expression plasmids and a glucocorticoid-responsive reporter gene demonstrated that the truncated nti receptor exhibits a reduced transcriptional regulatory activity. Gene fusions containing portions of both the wild-type and the nti GR-coding sequences were constructed and used to functionally map the nti receptor mutation. We found that the loss of the modulatory domain alone is sufficient to cause the observed defect in nti transcriptional transactivation. These results support the proposal that glucocorticoid-induced S49 cell death requires GR sequences which have previously been shown to be required for transcriptional regulation, suggesting that steroid-regulated apoptosis is controlled at the level of gene expression.

Original languageEnglish (US)
Pages (from-to)4574-4581
Number of pages8
JournalMolecular and Cellular Biology
Volume10
Issue number9
StatePublished - Sep 1990

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Glucocorticoid Receptors
Glucocorticoids
Steroids
Cell Death
Apoptosis
RNA Splicing
Molecular Models
Gene Fusion
Genetic Models
Reporter Genes
varespladib methyl
Transcriptional Activation
Molecular Biology
Exons
Lymphoma
Plasmids
Complementary DNA
Hormones
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

nti glucocorticoid receptor transcripts lack sequences encoding the amino-terminal transcriptional modulatory domain. / Dieken, Ellen S.; Meese, Eckart U.; Miesfeld, Roger.

In: Molecular and Cellular Biology, Vol. 10, No. 9, 09.1990, p. 4574-4581.

Research output: Contribution to journalArticle

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