Comprehensive Overview of the Structure and Regulation of the Glucocorticoid Receptor

Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternati...

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Bibliographic Details
Published inEndocrine reviews Vol. 35; no. 4; pp. 671 - 693
Main Authors Vandevyver, Sofie, Dejager, Lien, Libert, Claude
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.08.2014
Copyright by The Endocrine Society
Subjects
Allosteric properties
Alternative splicing
Animals
Composition effects
DNA structure
Gene Expression Regulation - physiology
Gene regulation
Glucocorticoid receptors
Glucocorticoids
Humans
Immunosuppressive agents
Inflammatory diseases
Isoforms
MicroRNAs - physiology
miRNA
Mutation - genetics
Nucleotide sequence
Post-transcription
Post-translation
Protein Isoforms - chemistry
Protein Isoforms - genetics
Protein Isoforms - physiology
Protein Processing, Post-Translational - physiology
Receptors
Receptors, Glucocorticoid - chemistry
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - physiology
Reviews
Transcription initiation
Transcription, Genetic - physiology
Translation initiation
Online AccessGet full text

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Abstract Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.
AbstractList Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.
Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the proteinʼs stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.
Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. There are several GR isoforms resulting from alternative RNA splicing and translation initiation of the GR transcript. Additionally, these isoforms are all subject to several transcriptional, post-transcriptional, and post-translational modifications, all of which affect the protein's stability and/or function. In this review, we summarize recent knowledge on the distinct GR isoforms and the processes that generate them. We also review the importance of all known transcriptional, post-transcriptional, and post-translational modifications, including the regulation of GR by microRNAs. Moreover, we discuss the crucial role of the putative GR-bound DNA sequence as an allosteric ligand influencing GR structure and activity. Finally, we describe how the differential composition and distinct regulation at multiple levels of different GR species could account for the wide and diverse effects of glucocorticoids.
Author Vandevyver, Sofie
Dejager, Lien
Libert, Claude
AuthorAffiliation Inflammation Research Center (S.V., L.D., C.L.), Flanders Institute for Biotechnology, B9052 Ghent, Belgium; and Department of Biomedical Molecular Biology (S.V., L.D., C.L.), Ghent University, B9052 Ghent, Belgium
AuthorAffiliation_xml – name: Inflammation Research Center (S.V., L.D., C.L.), Flanders Institute for Biotechnology, B9052 Ghent, Belgium; and Department of Biomedical Molecular Biology (S.V., L.D., C.L.), Ghent University, B9052 Ghent, Belgium
Author_xml – sequence: 1
  givenname: Sofie
  surname: Vandevyver
  fullname: Vandevyver, Sofie
  organization: 1Inflammation Research Center (S.V., L.D., C.L.), Flanders Institute for Biotechnology, B9052 Ghent, Belgium
– sequence: 2
  givenname: Lien
  surname: Dejager
  fullname: Dejager, Lien
  organization: 1Inflammation Research Center (S.V., L.D., C.L.), Flanders Institute for Biotechnology, B9052 Ghent, Belgium
– sequence: 3
  givenname: Claude
  surname: Libert
  fullname: Libert, Claude
  email: claude.libert@irc.vib-ugent.be
  organization: 1Inflammation Research Center (S.V., L.D., C.L.), Flanders Institute for Biotechnology, B9052 Ghent, Belgium
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24937701$$D View this record in MEDLINE/PubMed
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Snippet Glucocorticoids are among the most prescribed drugs worldwide for the treatment of numerous immune and inflammatory disorders. They exert their actions by...
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SubjectTerms Allosteric properties
Alternative splicing
Animals
Composition effects
DNA structure
Gene Expression Regulation - physiology
Gene regulation
Glucocorticoid receptors
Glucocorticoids
Humans
Immunosuppressive agents
Inflammatory diseases
Isoforms
MicroRNAs - physiology
miRNA
Mutation - genetics
Nucleotide sequence
Post-transcription
Post-translation
Protein Isoforms - chemistry
Protein Isoforms - genetics
Protein Isoforms - physiology
Protein Processing, Post-Translational - physiology
Receptors
Receptors, Glucocorticoid - chemistry
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - physiology
Reviews
Transcription initiation
Transcription, Genetic - physiology
Translation initiation
Title Comprehensive Overview of the Structure and Regulation of the Glucocorticoid Receptor
URI https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00003599-201408000-00004
https://www.ncbi.nlm.nih.gov/pubmed/24937701
https://www.proquest.com/docview/3129866618
https://www.proquest.com/docview/1547843628
Volume 35
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