Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation

Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of nuclear receptors (such as PPARs and RARs) engage in the formation of well-characterized 'typical' heterodimers with RXR. 'Atypi...

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Vydáno v:Nature reviews. Endocrinology Ročník 16; číslo 7; s. 363 - 377
Hlavní autoři: De Bosscher, Karolien, Desmet, Sofie J, Clarisse, Dorien, Estébanez-Perpiña, Eva, Brunsveld, Luc
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.07.2020
Témata:
Animals
Bile
Drugs
Gene expression
Hormones
Humans
Ligands
Medical innovations
Nuclear receptors
Peroxisome proliferator-activated receptors
Physiology
Protein Binding - physiology
Protein Multimerization - physiology
Proteins
Receptor Cross-Talk - physiology
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Cytoplasmic and Nuclear - physiology
Retinoid X receptors
Signal transduction
Signal Transduction - physiology
Therapies, Investigational - methods
Therapies, Investigational - trends
Transcription
Transcription Factors - metabolism
Transcription Factors - physiology
Vitamin E
ISSN:1759-5029, 1759-5037, 1759-5037
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Tagy: Přidat tag
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Abstract Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of nuclear receptors (such as PPARs and RARs) engage in the formation of well-characterized 'typical' heterodimers with RXR. 'Atypical' heterodimers (such as GR with PPARs, or PPAR with ERR) might form a novel class of physical complexes that might be more transient in nature. These heterodimers might harbour strong transcriptional flexibility, with no strict need for DNA binding of both partners. Direct crosstalk could stem from a pairwise physical association between atypical nuclear receptor heterodimers, either via pre-existing interaction pairs or via interactions that are newly induced with small molecules; such crosstalk might constitute an uncharted space to target nuclear receptor physiological and/or pathophysiological actions. In this Review, we discuss the emerging aspects of crosstalk in the nuclear receptor field and present various mechanistic crosstalk modes with examples that support applicability of the atypical heterodimer concept. Stabilization or disruption, in a context-dependent or cell type-dependent manner, of these more transient heterodimers is expected to fuel unprecedented translational approaches to yield novel therapeutic agents to treat major human diseases with higher precision.
AbstractList Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of nuclear receptors (such as PPARs and RARs) engage in the formation of well-characterized ‘typical’ heterodimers with RXR. ‘Atypical’ heterodimers (such as GR with PPARs, or PPAR with ERR) might form a novel class of physical complexes that might be more transient in nature. These heterodimers might harbour strong transcriptional flexibility, with no strict need for DNA binding of both partners. Direct crosstalk could stem from a pairwise physical association between atypical nuclear receptor heterodimers, either via pre-existing interaction pairs or via interactions that are newly induced with small molecules; such crosstalk might constitute an uncharted space to target nuclear receptor physiological and/or pathophysiological actions. In this Review, we discuss the emerging aspects of crosstalk in the nuclear receptor field and present various mechanistic crosstalk modes with examples that support applicability of the atypical heterodimer concept. Stabilization or disruption, in a context-dependent or cell type-dependent manner, of these more transient heterodimers is expected to fuel unprecedented translational approaches to yield novel therapeutic agents to treat major human diseases with higher precision.This Review discusses the emerging aspects of crosstalk in the nuclear receptor field. The authors present various mechanistic crosstalk modes and provide examples that support applicability of the atypical heterodimer concept.
Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of nuclear receptors (such as PPARs and RARs) engage in the formation of well-characterized 'typical' heterodimers with RXR. 'Atypical' heterodimers (such as GR with PPARs, or PPAR with ERR) might form a novel class of physical complexes that might be more transient in nature. These heterodimers might harbour strong transcriptional flexibility, with no strict need for DNA binding of both partners. Direct crosstalk could stem from a pairwise physical association between atypical nuclear receptor heterodimers, either via pre-existing interaction pairs or via interactions that are newly induced with small molecules; such crosstalk might constitute an uncharted space to target nuclear receptor physiological and/or pathophysiological actions. In this Review, we discuss the emerging aspects of crosstalk in the nuclear receptor field and present various mechanistic crosstalk modes with examples that support applicability of the atypical heterodimer concept. Stabilization or disruption, in a context-dependent or cell type-dependent manner, of these more transient heterodimers is expected to fuel unprecedented translational approaches to yield novel therapeutic agents to treat major human diseases with higher precision.
Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of nuclear receptors (such as PPARs and RARs) engage in the formation of well-characterized 'typical' heterodimers with RXR. 'Atypical' heterodimers (such as GR with PPARs, or PPAR with ERR) might form a novel class of physical complexes that might be more transient in nature. These heterodimers might harbour strong transcriptional flexibility, with no strict need for DNA binding of both partners. Direct crosstalk could stem from a pairwise physical association between atypical nuclear receptor heterodimers, either via pre-existing interaction pairs or via interactions that are newly induced with small molecules; such crosstalk might constitute an uncharted space to target nuclear receptor physiological and/or pathophysiological actions. In this Review, we discuss the emerging aspects of crosstalk in the nuclear receptor field and present various mechanistic crosstalk modes with examples that support applicability of the atypical heterodimer concept. Stabilization or disruption, in a context-dependent or cell type-dependent manner, of these more transient heterodimers is expected to fuel unprecedented translational approaches to yield novel therapeutic agents to treat major human diseases with higher precision.Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of nuclear receptors (such as PPARs and RARs) engage in the formation of well-characterized 'typical' heterodimers with RXR. 'Atypical' heterodimers (such as GR with PPARs, or PPAR with ERR) might form a novel class of physical complexes that might be more transient in nature. These heterodimers might harbour strong transcriptional flexibility, with no strict need for DNA binding of both partners. Direct crosstalk could stem from a pairwise physical association between atypical nuclear receptor heterodimers, either via pre-existing interaction pairs or via interactions that are newly induced with small molecules; such crosstalk might constitute an uncharted space to target nuclear receptor physiological and/or pathophysiological actions. In this Review, we discuss the emerging aspects of crosstalk in the nuclear receptor field and present various mechanistic crosstalk modes with examples that support applicability of the atypical heterodimer concept. Stabilization or disruption, in a context-dependent or cell type-dependent manner, of these more transient heterodimers is expected to fuel unprecedented translational approaches to yield novel therapeutic agents to treat major human diseases with higher precision.
Author Clarisse, Dorien
Brunsveld, Luc
Desmet, Sofie J
De Bosscher, Karolien
Estébanez-Perpiña, Eva
Author_xml – sequence: 1
  givenname: Karolien
  orcidid: 0000-0001-5059-9718
  surname: De Bosscher
  fullname: De Bosscher, Karolien
  email: Karolien.DeBosscher@vib-ugent.be
  organization: Translational Nuclear Receptor Research, VIB Center for Medical Biotechnology, UGent Department of Biomolecular Medicine, Gent, Belgium. Karolien.DeBosscher@vib-ugent.be
– sequence: 2
  givenname: Sofie J
  surname: Desmet
  fullname: Desmet, Sofie J
  organization: Translational Nuclear Receptor Research, VIB Center for Medical Biotechnology, UGent Department of Biomolecular Medicine, Gent, Belgium
– sequence: 3
  givenname: Dorien
  surname: Clarisse
  fullname: Clarisse, Dorien
  organization: Translational Nuclear Receptor Research, VIB Center for Medical Biotechnology, UGent Department of Biomolecular Medicine, Gent, Belgium
– sequence: 4
  givenname: Eva
  surname: Estébanez-Perpiña
  fullname: Estébanez-Perpiña, Eva
  organization: Laboratory of Structural Biology, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine (IBUB) of the University of Barcelona (UB), Barcelona, Spain
– sequence: 5
  givenname: Luc
  orcidid: 0000-0001-5675-511X
  surname: Brunsveld
  fullname: Brunsveld, Luc
  organization: Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Eindhoven, Netherlands
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32303708$$D View this record in MEDLINE/PubMed
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Snippet Nuclear receptor crosstalk can be defined as the interplay between different nuclear receptors or between their overlapping signalling pathways. A subset of...
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StartPage 363
SubjectTerms Animals
Bile
Drugs
Gene expression
Hormones
Humans
Ligands
Medical innovations
Nuclear receptors
Peroxisome proliferator-activated receptors
Physiology
Protein Binding - physiology
Protein Multimerization - physiology
Proteins
Receptor Cross-Talk - physiology
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Cytoplasmic and Nuclear - physiology
Retinoid X receptors
Signal transduction
Signal Transduction - physiology
Therapies, Investigational - methods
Therapies, Investigational - trends
Transcription
Transcription Factors - metabolism
Transcription Factors - physiology
Vitamin E
Title Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation
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