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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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.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.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.
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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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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