UDP-glucose-6-dehydrogenase (UGDH) is a cytosolic, hexameric enzyme that converts UDP-glucose to UDP-glucuronic acid (UDP-GlcUA), a key reaction in hormone and xenobiotic metabolism and in the production of extracellular matrix precursors. In this review, we classify UGDH as a molecular indicator of tumor progression in multiple cancer types, describe its involvement in key canonical cancer signaling pathways, and identify methods to inhibit UGDH, its substrates, and its downstream products. As such, we position UGDH as an enzyme to be exploited as a potential prognostication marker in oncology and a therapeutic target in cancer biology.
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http://dx.doi.org/10.18632/oncotarget.28514 | DOI Listing |
PLoS Genet
January 2025
Department of Biology, Boston University, Boston Massachusetts, United States of America.
The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China.
Epstein-Barr nuclear antigen 1 (EBNA1), a sequence-specific DNA binding protein of Epstein-Barr virus (EBV), is essential for viral genome replication and maintenance and is therefore an attractive target for the therapeutic intervention of EBV-associated cancers. Several EBNA1-specific inhibitors have demonstrated the ability to block EBNA1 function in vitro, but practical delivery strategies for these inhibitors in vivo are still lacking. Here, we report an intelligent hierarchical targeting theranostic nanosystem (denoted as mZGOCS@MnO-P5) that integrates an azide (N3) terminal dual-targeting peptide (N3-P5), a tumor microenvironment-responsive degradable MnO nanosheet, and a mesoporous ZnGaO:Cr, Sn near-infrared persistent luminescence (NIR-PL) nanosphere (mZGOCS).
View Article and Find Full Text PDFSci Immunol
January 2025
Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.
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