Evidence map›Paper›PMID 33510451›Full record

ArticleNature chemical biology2021

Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling.

Nelson E Bruno, Jerome C Nwachukwu, Sathish Srinivasan, Charles C Nettles, Tina Izard, Zhuang Jin, Jason Nowak, Michael D Cameron, Siddaraju V Boregowda, Donald G Phinney and 9 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Asymmetric allostery in estrogen receptor-α homodimers drives responses to the ensemble of estrogens in the hormonal milieu.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Illuminating ligand-induced dynamics in nuclear receptors through MD simulations.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024
    Review
  8. Review
  9. A structural mechanism of nuclear receptor biased agonism.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Article
  11. Structural insights into glucocorticoid receptor function.Biochemical Society transactions · 2021
    Review
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Nelson E BrunoDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Jerome C NwachukwuDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0003-4313-9187
Sathish SrinivasanDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Charles C NettlesDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Tina IzardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Zhuang JinDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0002-8031-5680
Jason NowakDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Michael D CameronDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0003-3154-4775
Siddaraju V BoregowdaDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
Donald G PhinneyDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0002-8688-2619
Olivier ElementoCaryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Xu LiuDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Eric A OrtlundDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-8855-3029
René HoutmanDepartment of Research and Development, PamGene, 's-Hertogenbosch, the Netherlands.ORCID http://orcid.org/0000-0001-7639-6310
Diana A StavrevaLaboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD, USA.
Gordon L HagerLaboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD, USA.
Theodore M KameneckaDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
Douglas J KojetinDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0001-8058-6168
Kendall W NettlesDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA. knettles@scripps.edu.ORCID http://orcid.org/0000-0003-2917-7574

Funding

Function of Steroid Receptors in Subcellular CompartmentsZIABC010027 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HAGER, GORDON L · 2009 to 2025
$8.7M
Mechanistic studies of corepressor-mediated PPARγ transcriptional repressionR01DK124870 · NIDDK · VANDERBILT UNIVERSITY · PI KOJETIN, DOUGLAS · 2020 to 2023
$1.9M
NIDDK NIH HHS R01 DK124870
6 · The paper itself

Abstract

Glucocorticoids display remarkable anti-inflammatory activity, but their use is limited by on-target adverse effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach, ligand class analysis, to examine ligands designed to modulate glucocorticoid receptor activity through distinct structural mechanisms. These ligands displayed diverse activity profiles, providing the variance required to identify target genes and coregulator interactions that were highly predictive of their effects on myocyte glucose disposal and protein balance. Their anti-inflammatory effects were linked to glucose disposal but not muscle atrophy. This approach also predicted selective modulation in vivo, identifying compounds that were muscle-sparing or anabolic for protein balance and mitochondrial potential. Ligand class analysis defined the mechanistic links between the ligand-receptor interface and ligand-driven physiological outcomes, a general approach that can be applied to any ligand-regulated allosteric signaling system.

Indexed as

A549 CellsAllosteric RegulationAnimalsAnti-Inflammatory AgentsCell Line, TransformedGene Expression RegulationGlucoseGlucose Transporter Type 4HumansLipopolysaccharidesMaleMembrane Potential, MitochondrialMiceMice, Inbred C57BLMitochondriaMuscle Fibers, SkeletalAnti-Inflammatory AgentsGlucoseGlucose Transporter Type 4LipopolysaccharidesReceptors, GlucocorticoidSlc2a4 protein, mouse

Identifiers

PMID33510451
PMCPMC8783757

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.