William Bourguet
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View article: New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands, and transcriptional coregulators
New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands, and transcriptional coregulators Open
Retinoic acid receptors (RARs) are ligand-dependent transcription factors essential for various biological processes, including embryogenesis, differentiation, and apoptosis. RARs function as heterodimers with retinoid X receptors (RXRs) a…
View article: Distinct 2-phenyl-imidazo[1, 2α] pyridine derivatives drive ER degradation and selectively impair proliferation of ER<sup>+</sup> breast cancer cells via the aryl hydrocarbon receptor
Distinct 2-phenyl-imidazo[1, 2α] pyridine derivatives drive ER degradation and selectively impair proliferation of ER<sup>+</sup> breast cancer cells via the aryl hydrocarbon receptor Open
X15695 is a 2-phenyl-imidazo[1, 2α] pyridine derivative identified as an orally active, selective oestrogen receptor (ER) degrader that inhibits the proliferation of ER + breast cancer cells. Here, we show that X15695 is an aryl hydrocarbo…
View article: New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands and transcriptional coregulators
New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands and transcriptional coregulators Open
Retinoic acid receptors (RARs) are ligand-dependent transcription factors essential for various biological processes, including embryogenesis, differentiation, and apoptosis. RARs function as heterodimers with retinoid X receptors (RXRs) a…
View article: A two-in-one expression construct for biophysical and structural studies of the human pregnane X receptor ligand-binding domain, a pharmaceutical and environmental target
A two-in-one expression construct for biophysical and structural studies of the human pregnane X receptor ligand-binding domain, a pharmaceutical and environmental target Open
The ligand-binding domain (LBD) of the human nuclear receptor pregnane X receptor (PXR) is known to crystallize in two different crystal forms, P 2 1 2 1 2 1 or P 4 3 2 1 2, depending on the construct and the strategy used for protein prod…
View article: An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice
An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice Open
The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their acti…
View article: What Structural Biology Tells Us About the Mode of Action and Detection of Toxicants
What Structural Biology Tells Us About the Mode of Action and Detection of Toxicants Open
The study of the adverse effects of chemical substances on living organisms is an old and intense field of research. However, toxicological and environmental health sciences have long been dominated by descriptive approaches that enable as…
View article: A potent agonist-based PROTAC targeting Pregnane X Receptor that delays colon cancer relapse
A potent agonist-based PROTAC targeting Pregnane X Receptor that delays colon cancer relapse Open
Tumor recurrence is often attributed to drug-tolerant cancer stem cells. We previously demonstrated that down regulation of the Pregnane X Receptor (PXR, NR1I2) decreases chemoresistance of cancer stem cells and prevents colorectal cancer …
View article: Corrigendum: Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project
Corrigendum: Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project Open
[This corrects the article DOI: 10.3389/ftox.2023.1212509.].
View article: Structural Insights into the Activation of Human Aryl Hydrocarbon Receptor by the Environmental Contaminant Benzo[a]pyrene and Structurally Related Compounds
Structural Insights into the Activation of Human Aryl Hydrocarbon Receptor by the Environmental Contaminant Benzo[a]pyrene and Structurally Related Compounds Open
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor belonging to the bHLH/PAS protein family and responding to hundreds of natural and chemical substances. It is primarily involved in the defense against chemical…
View article: Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project
Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project Open
In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. Mor…
View article: 2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors
2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors Open
2,4-Di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. We asked whether …
View article: 2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors
2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors Open
2,4-di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. Here we asked whe…
View article: Design and in vitro characterization of RXR variants as tools to investigate the biological role of endogenous rexinoids
Design and in vitro characterization of RXR variants as tools to investigate the biological role of endogenous rexinoids Open
Retinoid X receptors (RXRα, β, and γ) are essential members of the nuclear receptor (NR) superfamily of ligand-dependent transcriptional regulators that bind DNA response elements and control the expression of large gene networks. As oblig…
View article: Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex
Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex Open
Summary Living organisms have developed protein sensors helping them to adapt to their environment 1 . The aryl hydrocarbon receptor (AHR) is an emblematic member of this class of proteins, and a ligand-dependent transcription factor that …
View article: Structure-Based and Knowledge-Informed Design of B-Raf Inhibitors Devoid of Deleterious PXR Binding
Structure-Based and Knowledge-Informed Design of B-Raf Inhibitors Devoid of Deleterious PXR Binding Open
Dabrafenib is an anticancer drug currently used in the clinics, alone or in combination. However, dabrafenib was recently shown to potently activate the human nuclear receptor pregnane X receptor (PXR). PXR activation increases the clearan…
View article: Ligands and DNA in the allosteric control of retinoid receptors function
Ligands and DNA in the allosteric control of retinoid receptors function Open
Retinoids are a family of compounds that include both vitamin A (all-trans retinol) and its naturally occurring metabolites such as retinoic acids (e.g. all-trans retinoic acid) as well as synthetic analogs. They are critically involved in…
View article: Functional analyses of phosphatidylserine/PI(4)P exchangers with diverse lipid species and membrane contexts set unanticipated rules on lipid transfer
Functional analyses of phosphatidylserine/PI(4)P exchangers with diverse lipid species and membrane contexts set unanticipated rules on lipid transfer Open
Several members of the oxysterol-binding protein-related proteins (ORPs)/oxysterol-binding homology (Osh) family exchange phosphatidylserine (PS) and phosphatidylinositol 4-phosphate (PI(4)P) at the endoplasmic reticulum/plasma membrane (P…
View article: A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids Using In Vitro Reporter Gene Assays
A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids Using In Vitro Reporter Gene Assays Open
The nuclear receptor pregnane X receptor (PXR) is a ligand-dependent transcription factor that regulates genes involved in xenobiotic metabolism in mammals. Many studies suggest that PXR may play a similar role in fish. The interaction of …
View article: Mechanistic insights into the synergistic activation of the RXR–PXR heterodimer by endocrine disruptor mixtures
Mechanistic insights into the synergistic activation of the RXR–PXR heterodimer by endocrine disruptor mixtures Open
Significance Many environmental pollutants act as endocrine disruptors that interfere with normal endocrine regulation and promote adverse effects in humans. As a major target of xenobiotics, the pregnane X receptor (PXR) is known to play …
View article: Structural insights into the cooperative interaction of the intrinsically disordered co-activator TIF2 with retinoic acid receptor heterodimer (RXR/RAR)
Structural insights into the cooperative interaction of the intrinsically disordered co-activator TIF2 with retinoic acid receptor heterodimer (RXR/RAR) Open
Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers that activate target gene transcription by recruiting co-activator complexes in response to ligand binding. The nuclear receptor (NR) co-activator TIF2 mediat…
View article: Human and Zebrafish Nuclear Progesterone Receptors Are Differently Activated by Manifold Progestins
Human and Zebrafish Nuclear Progesterone Receptors Are Differently Activated by Manifold Progestins Open
The environmental risk of natural and synthetic ligands of the nuclear progesterone receptor (nPR) has been pointed out, however there is still a lack of mechanistic information regarding their ability to interact with nuclear PR in aquati…
View article: High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor
High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor Open
Prostate cancer is the most commonly diagnosed malignancy in men. Its growth mainly relies on the activity of the androgen receptor (AR), justifying the use of androgen deprivation therapy as a gold standard treatment for the metastatic di…
View article: Peroxisome proliferator‐activated receptor gamma‐ligand‐binding domain mutations associated with familial partial lipodystrophy type 3 disrupt human trophoblast fusion and fibroblast migration
Peroxisome proliferator‐activated receptor gamma‐ligand‐binding domain mutations associated with familial partial lipodystrophy type 3 disrupt human trophoblast fusion and fibroblast migration Open
The transcription factor peroxisome proliferator‐activated receptor gamma (PPARG) is essential for placental development, and alterations in its expression and/or activity are associated with human placental pathologies such as pre‐eclamps…
View article: The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds
The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds Open
The purpose of this project report is to introduce the European “GOLIATH” project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of m…