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Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.
Nature
January 2025
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.
View Article and Find Full Text PDFTgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation to Promote SASP in Senescent Microglia.
Aging Cell
January 2025
MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
Microglia, as resident immune cells in the central nervous system (CNS), play a crucial role in maintaining homeostasis and phagocytosing metabolic waste in the brain. Senescent microglia exhibit decreased phagocytic capacity and increased neuroinflammation through senescence-associated secretory phenotype (SASP). This process contributes to the development of various neurodegenerative diseases, including Alzheimer's disease (AD).
View Article and Find Full Text PDFcGAS/STING in skin melanoma: from molecular mechanisms to therapeutics.
Cell Commun Signal
November 2024
Department of Food Nutrition and Safety, Dalian Medical University, Dalian, 116044, China.
Melanoma, recognized as the most aggressive type of skin cancer, has experienced a notable increase in cases, especially within populations with fair skin. This highly aggressive cancer is largely driven by UV radiation exposure, resulting in the uncontrolled growth and malignant transformation of melanocytes. The cGAS-STING pathway, an immune signaling mechanism responsible for detecting double-stranded DNA in the cytoplasm, is essential for mediating the immune response against melanoma.
View Article and Find Full Text PDFTransglutaminase 2 in breast cancer metastasis and drug resistance.
Front Cell Dev Biol
October 2024
Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Transglutaminase 2 (TG2) is a widely distributed multifunctional protein with various enzymatic and non-enzymatic activities. It is becoming increasingly evident that high levels of TG2 in tumors induce the occurrence of epithelial to mesenchymal transition (EMT) and the acquisition of stem cell-like phenotypes, promoting tumor metastasis and drug resistance. By regulating intracellular and extracellular signaling pathways, TG2 promotes breast cancer metastasis to lung, brain, liver and bone, as well as resistance to various chemotherapy drugs including docetaxel, doxorubicin, platinum and neratinib.
View Article and Find Full Text PDFInitial Characterization of WDR5B Reveals a Role in the Proliferation of Retinal Pigment Epithelial Cells.
Cells
July 2024
Department of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
The chromatin-associated protein WDR5 has been widely studied due to its role in histone modification and its potential as a pharmacological target for the treatment of cancer. In humans, the protein with highest sequence homology to WDR5 is encoded by the retrogene WDR5B, which remains unexplored. Here, we used CRISPR-Cas9 genome editing to generate WDR5B knockout and WDR5B-FLAG knock-in cell lines for further characterization.
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