Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Molecular Biology of Nuclear Receptors 3.0
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Molecular Biology of Nuclear Receptors 3.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 13155

Special Issue Editors

Prof. Dr. Akira Sugawara

E-Mail Website
Guest Editor
Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
Interests: elucidation of the involvement of nuclear receptors in the etiology of endocrine/metabolic disorders; innovation of novel drugs against endocrine/metabolic disorders by targeting nuclear receptors; identification of co-factors; post-translational modifications of nuclear receptors by LC/MS/MS
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Makoto Makishima

E-Mail Website
Guest Editor
Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
Interests: regulation of lipid metabolism and immunity by nuclear receptors in the liver and intestine; molecular basis of function-selective nuclear receptor ligands and application to drug discovery; regulation of xenobiotic metabolisms and their relationship to human disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue “Molecular Biology of Nuclear Receptors” and Special Issue "Molecular Biology of Nuclear Receptors 2.0".

Nuclear receptors include steroid/thyroid hormone receptors, metabolic sensors and orphan receptors. Metabolic sensor-type nuclear receptors, such as liver X receptor, farnesoid X receptor and peroxisome proliferator activator receptor (PPAR), are activated by oxysterol, bile acid and fatty acid, and regulate their metabolism. These receptors, like steroid hormone receptors, also regulate cellular proliferation/differentiation, and immunity. Dysregulation in these systems has been implicated in the pathogenesis of human diseases, such as cancer, cardiovascular disease, and inflammation. Moreover, nuclear receptors including PPAR, retinoid receptors, and several orphan receptors have recently been known to be involved in the etiology of metabolic syndrome and atherosclerosis. In this Special Issue, we are pleased to invite original manuscripts focusing on the relationships between nuclear receptors and human disorders, as well as novel drug innovation.

Prof. Dr. Akira Sugawara
Prof. Dr. Makoto Makishima
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Related Special Issues

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

11 pages, 1399 KiB  
Article
The Cytoskeletal Protein Zyxin Inhibits Retinoic Acid Signaling by Destabilizing the Maternal mRNA of the RXRγ Nuclear Receptor
by Elena A. Parshina, Eugeny E. Orlov, Andrey G. Zaraisky and Natalia Y. Martynova
Int. J. Mol. Sci. 2022, 23(10), 5627; https://doi.org/10.3390/ijms23105627 - 17 May 2022
Viewed by 1865
Abstract
Zyxin is an LIM-domain-containing protein that regulates the assembly of F-actin filaments in cell contacts. Additionally, as a result of mechanical stress, Zyxin can enter nuclei and regulate gene expression. Previously, we found that Zyxin could affect mRNA stability of the maternally derived [...] Read more.
Zyxin is an LIM-domain-containing protein that regulates the assembly of F-actin filaments in cell contacts. Additionally, as a result of mechanical stress, Zyxin can enter nuclei and regulate gene expression. Previously, we found that Zyxin could affect mRNA stability of the maternally derived stemness factors of Pou5f3 family in Xenopus laevis embryos through binding to Y-box factor1. In the present work, we demonstrate that Zyxin can also affect mRNA stability of the maternally derived retinoid receptor Rxrγ through the same mechanism. Moreover, we confirmed the functional link between Zyxin and Rxrγ-dependent gene expression. As a result, Zyxin appears to play an essential role in the regulation of the retinoic acid signal pathway during early embryonic development. Besides, our research indicates that the mechanism based on the mRNA destabilization by Zyxin may take part in the control of the expression of a fairly wide range of maternal genes. Full article
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors 3.0)
►▼ Show Figures

Graphical abstract

21 pages, 5345 KiB  
Article
The T850D Phosphomimetic Mutation in the Androgen Receptor Ligand Binding Domain Enhances Recruitment at Activation Function 2
by Christine Helsen, Tien Nguyen, Thomas Vercruysse, Staf Wouters, Dirk Daelemans, Arnout Voet and Frank Claessens
Int. J. Mol. Sci. 2022, 23(3), 1557; https://doi.org/10.3390/ijms23031557 - 29 Jan 2022
Cited by 3 | Viewed by 2111
Abstract
Several key functions of the androgen receptor (AR) such as hormone recognition and co-regulator recruitment converge in the ligand binding domain (LBD). Loss- or gain-of-function of the AR contributes to pathologies such as the androgen insensitivity syndrome and prostate cancer. Here, we describe [...] Read more.
Several key functions of the androgen receptor (AR) such as hormone recognition and co-regulator recruitment converge in the ligand binding domain (LBD). Loss- or gain-of-function of the AR contributes to pathologies such as the androgen insensitivity syndrome and prostate cancer. Here, we describe a gain-of-function mutation of the surface-exposed threonine at position 850, located at the amino-terminus of Helix 10 (H10) in the AR LBD. Since T850 phosphorylation was reported to affect AR function, we created the phosphomimetic mutation T850D. The AR T850D variant has a 1.5- to 2-fold increased transcriptional activity with no effect on ligand affinity. In the androgen responsive LNCaP cell line grown in medium with low androgen levels, we observed a growth advantage for cells in which the endogenous AR was replaced by AR T850D. Despite the distance to the AF2 site, the AR T850D LBD displayed an increased affinity for coactivator peptides as well as the 23FQNLF27 motif of AR itself. Molecular Dynamics simulations confirm allosteric transmission of the T850D mutation towards the AF2 site via extended hydrogen bond formation between coactivator peptide and AF2 site. This mechanistic study thus confirms the gain-of-function character of T850D and T850 phosphorylation for AR activity and reveals details of the allosteric communications within the LBD. Full article
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors 3.0)
►▼ Show Figures

Figure 1

26 pages, 6692 KiB  
Article
Predicting Potential Endocrine Disrupting Chemicals Binding to Estrogen Receptor α (ERα) Using a Pipeline Combining Structure-Based and Ligand-Based in Silico Methods
by Asma Sellami, Matthieu Montes and Nathalie Lagarde
Int. J. Mol. Sci. 2021, 22(6), 2846; https://doi.org/10.3390/ijms22062846 - 11 Mar 2021
Cited by 5 | Viewed by 3145
Abstract
The estrogen receptors α (ERα) are transcription factors involved in several physiological processes belonging to the nuclear receptors (NRs) protein family. Besides the endogenous ligands, several other chemicals are able to bind to those receptors. Among them are endocrine disrupting chemicals (EDCs) that [...] Read more.
The estrogen receptors α (ERα) are transcription factors involved in several physiological processes belonging to the nuclear receptors (NRs) protein family. Besides the endogenous ligands, several other chemicals are able to bind to those receptors. Among them are endocrine disrupting chemicals (EDCs) that can trigger toxicological pathways. Many studies have focused on predicting EDCs based on their ability to bind NRs; mainly, estrogen receptors (ER), thyroid hormones receptors (TR), androgen receptors (AR), glucocorticoid receptors (GR), and peroxisome proliferator-activated receptors gamma (PPARγ). In this work, we suggest a pipeline designed for the prediction of ERα binding activity. The flagged compounds can be further explored using experimental techniques to assess their potential to be EDCs. The pipeline is a combination of structure based (docking and pharmacophore models) and ligand based (pharmacophore models) methods. The models have been constructed using the Environmental Protection Agency (EPA) data encompassing a large number of structurally diverse compounds. A validation step was then achieved using two external databases: the NR-DBIND (Nuclear Receptors DataBase Including Negative Data) and the EADB (Estrogenic Activity DataBase). Different combination protocols were explored. Results showed that the combination of models performed better than each model taken individually. The consensus protocol that reached values of 0.81 and 0.54 for sensitivity and specificity, respectively, was the best suited for our toxicological study. Insights and recommendations were drawn to alleviate the screening quality of other projects focusing on ERα binding predictions. Full article
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors 3.0)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

20 pages, 1320 KiB  
Review
Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
by Takeshi Katafuchi and Makoto Makishima
Int. J. Mol. Sci. 2022, 23(11), 6046; https://doi.org/10.3390/ijms23116046 - 27 May 2022
Cited by 42 | Viewed by 5325
Abstract
Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the [...] Read more.
Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones. Farnesoid X receptor (FXR) is a nuclear receptor that forms a heterodimer with retinoid X receptor α (RXRα), is activated by BAs in the enterohepatic circulation reabsorbed via transporters in the ileum and the colon, and plays a critical role in regulating gene expression involved in cholesterol, BA, and lipid metabolism in the liver. The FXR/RXRα heterodimer also exists in the distal ileum and regulates production of fibroblast growth factor (FGF) 15/FGF19, a hormone traveling via the enterohepatic circulation that activates hepatic FGF receptor 4 (FGFR4)-β-klotho receptor complex and regulates gene expression involved in cholesterol, BA, and lipid metabolism, as well as those regulating cell proliferation. Agonists for FXR and analogs for FGF15/19 are currently recognized as a promising therapeutic target for metabolic syndrome and cholestatic diseases. Full article
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors 3.0)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop