Human glucocorticoid receptor isoform β

RRRRecent understanding of its potential implications in physiology and pathophysiology

Tomoshige Kino, Yan A. Su, George P. Chrousos

Research output: Contribution to journalReview article

95 Citations (Scopus)

Abstract

The human glucocorticoid receptor (GR) gene expresses two splicing isoforms α and β through alternative use of specific exons 9α and 9β. In contrast to the classic receptor GRα, which mediates most of the known actions of glucocorticoids, the functions of GRβ have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRβ. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRα-mediated transcriptional activity. A recent report suggested that the "ligand-binding domain" of GRβ is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRβ, its mechanisms of action, and its pathologic implications.

Original languageEnglish
Pages (from-to)3435-3448
Number of pages14
JournalCellular and Molecular Life Sciences
Volume66
Issue number21
DOIs
Publication statusPublished - Nov 2009
Externally publishedYes

Fingerprint

Glucocorticoid Receptors
Protein Isoforms
Glucocorticoids
Ligands
Mifepristone
Genes
Exons
Fluorescence

Keywords

  • Cytoplasmic to nuclear translocation
  • Glucocorticoid receptor
  • Ligand-binding pocket
  • Microarray
  • Splicing isoform
  • Zebrafish

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Human glucocorticoid receptor isoform β : RRRRecent understanding of its potential implications in physiology and pathophysiology. / Kino, Tomoshige; Su, Yan A.; Chrousos, George P.

In: Cellular and Molecular Life Sciences, Vol. 66, No. 21, 11.2009, p. 3435-3448.

Research output: Contribution to journalReview article

@article{f9bc13daccde46a88acdf6877d41ac29,
title = "Human glucocorticoid receptor isoform β: RRRRecent understanding of its potential implications in physiology and pathophysiology",
abstract = "The human glucocorticoid receptor (GR) gene expresses two splicing isoforms α and β through alternative use of specific exons 9α and 9β. In contrast to the classic receptor GRα, which mediates most of the known actions of glucocorticoids, the functions of GRβ have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRβ. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRα-mediated transcriptional activity. A recent report suggested that the {"}ligand-binding domain{"} of GRβ is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRβ, its mechanisms of action, and its pathologic implications.",
keywords = "Cytoplasmic to nuclear translocation, Glucocorticoid receptor, Ligand-binding pocket, Microarray, Splicing isoform, Zebrafish",
author = "Tomoshige Kino and Su, {Yan A.} and Chrousos, {George P.}",
year = "2009",
month = "11",
doi = "10.1007/s00018-009-0098-z",
language = "English",
volume = "66",
pages = "3435--3448",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "21",

}

TY - JOUR

T1 - Human glucocorticoid receptor isoform β

T2 - RRRRecent understanding of its potential implications in physiology and pathophysiology

AU - Kino, Tomoshige

AU - Su, Yan A.

AU - Chrousos, George P.

PY - 2009/11

Y1 - 2009/11

N2 - The human glucocorticoid receptor (GR) gene expresses two splicing isoforms α and β through alternative use of specific exons 9α and 9β. In contrast to the classic receptor GRα, which mediates most of the known actions of glucocorticoids, the functions of GRβ have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRβ. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRα-mediated transcriptional activity. A recent report suggested that the "ligand-binding domain" of GRβ is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRβ, its mechanisms of action, and its pathologic implications.

AB - The human glucocorticoid receptor (GR) gene expresses two splicing isoforms α and β through alternative use of specific exons 9α and 9β. In contrast to the classic receptor GRα, which mediates most of the known actions of glucocorticoids, the functions of GRβ have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRβ. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRα-mediated transcriptional activity. A recent report suggested that the "ligand-binding domain" of GRβ is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRβ, its mechanisms of action, and its pathologic implications.

KW - Cytoplasmic to nuclear translocation

KW - Glucocorticoid receptor

KW - Ligand-binding pocket

KW - Microarray

KW - Splicing isoform

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=70349881524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349881524&partnerID=8YFLogxK

U2 - 10.1007/s00018-009-0098-z

DO - 10.1007/s00018-009-0098-z

M3 - Review article

VL - 66

SP - 3435

EP - 3448

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 21

ER -