Coregulator recruitment to nuclear receptors (NRs) and other transcription factors is essential for proper metabolic gene regulation, with coactivators enhancing and corepressors attenuating gene transcription. The steroid receptor coactivator (SRC) family is composed of three homologous members (SRC-1, SRC-2, and SRC-3), which are uniquely important for mediating steroid hormone and mitogenic actions. An accumulating body of work highlights the diverse array of metabolic functions regulated by the SRCs, including systemic metabolite homeostasis, inflammation, and energy regulation. We discuss here the cooperative and unique functions among the SRCs to provide a comprehensive atlas of systemic SRC metabolic regulation. Deciphering the fractional and synergistic contributions of the SRCs to metabolic homeostasis is crucial to understanding fully the networks underlying metabolic transcriptional regulation.
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http://dx.doi.org/10.1016/j.tem.2014.05.004 | DOI Listing |
Breast Cancer Res
January 2025
Department of Cancer Biology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, 50153, USA.
Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
The benefit of adjuvant chemotherapy (CT) for hormone receptor-negative T1a and T1bN0M0 breast cancer remains uncertain. Our study was to explore prognostic value and identify candidates of adjuvant CT for these patients. The data of hormone receptor-negative T1a and T1bN0M0 breast cancer patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
January 2025
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. Electronic address:
It is well known that vitamin D is essential for human health; however, many people suffer from vitamin D deficiency or insufficiency worldwide, including in Japan. Serum 25-hydroxyvitamin D (25(OH)D) concentrations are typically measured to evaluate vitamin D status. In a previous study, we demonstrated that the concentrations of vitamin D metabolites in urine, measured using the NLucVDR assay system composed of a split-type nanoluciferase and the ligand-binding domain (LBD) of the human vitamin D receptor, correlated with serum 25(OH)D concentrations measured using liquid chromatography-mass spectrometry (LC-MS) or electrochemiluminescence immunoassays (ECLIAs).
View Article and Find Full Text PDFLiver Int
February 2025
Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, China.
Background: Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear.
Methods: We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE.
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