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Cited by 1,200Nuclear Receptors and SignalingRetinoids in leukemia and cellular processesEstrogen and related hormone effects

Nuclear Receptors, RXR, and the Big Bang

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Evans, Ronald M., Mangelsdorf, David J.·2014·Cell
DOI 10.1016/j.cell.2014.03.012PMC PMC4029515
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Abstract

Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism.

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  • LXRs (LXRβ and LXRα) are nuclear hormone receptor transcription factors that drive transcriptional activation of Apoe, as well as other genes involved in cholesterol, fatty acid, and glucose metabolism.

    “Liver-X receptors (LXRβ and LXRα) are members of the nuclear hormone receptor family of transcription factors that drive transcriptional activation of Apoe, as well as other genes involved in cholesterol, fatty acid, and glucose metabolism”

    From LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer (2018) · cites this paper as Evans and Mangelsdorf, 2014

    The “What’s My Ligand?” section identifies LXRs as nuclear receptors involved in sterol homeostasis, and “Engaging the Energy Vector” says LXR activation promotes lipogenesis and up-regulates a gene network for cholesterol removal. Our copy does not identify Apoe as an LXR target or say that LXRs activate genes involved in glucose metabolism; the passages have no page numbers. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Evans, R. M., & Mangelsdorf, D. J.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Evans, Ronald M.
  • Mangelsdorf, David J.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2014-03
Volume
157
Issue
1
Pages
255-266
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2014.03.012
PMC
PMC4029515
OpenAlex
W2072822958
Cited by
1,200
References
12
Citations by year
2026: 80 · 2025: 103 · 2024: 81 · 2023: 102 · 2022: 101 · 2021: 122 · 2020: 133 · 2019: 96 · 2018: 95 · 2017: 94 · 2016: 81 · 2015: 81 · 2014: 28 · 2013: 1
FWCI
10.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Heart, Lung, and Blood Institute (HL105278, R01HL105278, HL-088093, P01HL088093)
  • National Cancer Institute (CA014195, P30CA014195)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R37DK057978, DK057978, R01DK057978, R24DK090962, DK090962, R01DK067158)
  • National Institute of Environmental Health Sciences (P42ES010337, ES 010337)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
nuclear receptors, retinoid X receptor, orphan receptors, steroid hormone receptors, retinoid receptors, vitamin D receptor, thyroid hormone receptor, receptor evolution, ligand binding, transcriptional regulation, signaling networks, molecular endocrinology
MeSH terms
Animals, Endocrinology, Gene Expression Regulation, Humans, Transcription, Genetic, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Retinoid X Receptors

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