A new transcript splice variant of the human glucocorticoid receptor: Identification and tissue distribution of hGRΔ313-338, an alternative exon 2 transactivation domain isoform

Jonathan D. Turner*, Andrea B. Schote, Marc Keipes, Claude P. Muller

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

24 Citations (Scopus)

Abstract

All human glucocorticoid receptor (hGR) isoforms are encoded by the NR3C1 gene consisting of seven core exons (exons 2-8) common to all protein isoforms. The gene has two major exon 8-9 splice variants and a 5′-UTR consisting of 11 alternative splice variants. The N-terminal region of the hGR includes a tau 1 transactivation domain that interacts with proteins in the basal transcriptional apparatus, including the TATA box-binding protein. Here, we report the existence and the tissue distribution of a novel splice variant, hGRΔ313-338, with a 26 residue (78 bp) deletion in this N-terminal region encoded by exon 2, between amino acids 313 and 338. The hGRΔ313-338 observed at them RNA level represents a transcript variant encoding a smaller protein isoform detected by WB with a predicted deletion between the tau 1 domain and the DNA-binding domain (DBD) encoded by exons 3 and 4. Previous studies in transgenic mice showed that the removal of the entire exon 2 covering both the tau 1 transactivation domain and our deleted region produced a functional receptor albeit with an altered glucocorticoid-induced gene transcription pattern. Interestingly, the deleted residues show a number of potential phosphorylation sites including serine 317, known to be phosphorylated. It is thought that phosphorylation plays an important role in transactivation action of hGR. Thus, we hypothesize that hGRΔ313-338 represents a hGR isoform with an altered glucocorticoid-induced transactivation profile.

Original languageEnglish
Title of host publicationSignal Transduction Pathways, Part C
Subtitle of host publicationCell Signaling in Health and Disease
PublisherBlackwell Publishing Inc.
Pages334-341
Number of pages8
ISBN (Print)1573316954, 9781573316958
DOIs
Publication statusPublished - Jan 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1095
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Glucocorticoid receptor
  • Isoform
  • Splice variant

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