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Non-canonical hepatic androgen receptor mediates glucagon sensitivity in female mice through the PGC1α/ERRα/mitochondria axis.
Cell Rep
January 2025
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Glucagon has recently been found to modulate liver fat content, in addition to its role in regulating gluconeogenesis. However, the precise mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. By employing chemical and genetic approaches, we demonstrate that inhibiting the androgen receptor (AR) impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes and female mice.
View Article and Find Full Text PDFInterplay between Cα Methylation and Cα Stereochemistry in the Folding Energetics of a Helix-Rich Miniprotein.
Chembiochem
January 2025
University of Pittsburgh, Department of Chemistry, 219 Parkman Ave., 15260, Pittsburgh, UNITED STATES OF AMERICA.
The α-helix is an abundant and functionally important element of protein secondary structure, which has motivated intensive efforts toward chemical strategies to stabilize helical folds. One such method is the incorporation of non-canonical backbone composition through an additional methyl substituent at the Cα atom. Examples of monomers include the achiral 2-aminoisobutyric acid (Aib) with geminal dimethyl substitution and chiral analogues with one methyl and one non-methyl substituent.
View Article and Find Full Text PDFOligostyrylbenzene Derivatives with Antiparasitic and Antibacterial Activity as Potent G-Quadruplex Ligands.
Molecules
December 2024
Departamento de Bioquímica y Farmacología Molecular, Instituto de Parasitología y Biomedicina López Neyra, CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Spain.
G-quadruplexes (G4s) are non-canonical secondary structures that play a crucial role in the regulation of genetic expression. This study explores the interaction between G4s and a small family of oligostyrylbenzene (OSB) derivatives, characterized by tris(styryl)benzene and tetrastyrylbenzene backbones, functionalized with either trimethylammonium or 1-methylpyridinium groups. Initially identified as DNA ligands, these OSB derivatives have now been recognized as potent G4 binders, surpassing in binding affinity commercially available ligands such as pyridostatin and displaying good selectivity for G4s over duplex DNA.
View Article and Find Full Text PDFTCF12 and LncRNA MALAT1 Cooperatively Harness High Cyclin D1 but Low β-Catenin Gene Expression to Exacerbate Colorectal Cancer Prognosis Independently of Metastasis.
Cells
December 2024
Graduate Program of Biotechnology in Medicine, National Health Research Institutes, National Tsing Hua University, Hsinchu City 300, Taiwan.
Metastasis is a well-known factor worsening colorectal cancer (CRC) prognosis, but mortality mechanisms in non-metastatic patients with poor outcomes are less understood. TCF12 is a transcription factor that can be physically associated with the long non-coding RNA MALAT1, creating an alliance with correlated expression levels in CRC patients. This TCF12-MALAT1 alliance is linked to poorer prognosis independently of age and metastasis.
View Article and Find Full Text PDFA Novel Mechanism for Transcription Termination in the Locus of .
Biology (Basel)
November 2024
Department of Regulation of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow 119334, Russia.
This study investigated an alternative mechanism of transcription termination that occurs independently of polyadenylation. We focused on a non-canonical transcription terminator (NTT) identified in the gene of . Using a developed model system, we demonstrated that the minimal functional unit of the NTT consists of 79 nucleotides that form a specific secondary RNA structure.
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