PGG: A Dual-Action Natural Compound that Degrades MAT2A to Trigger Pyroptosis and Boost Anti-Tumor Immunity (IMAGE)
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Analyses of high-throughput screening and biochemical examines reveal that the natural compound PGG employs a potent "dual-mechanism " inhibition on MAT2A. It not only blocks the enzyme's activity but also tags it for destruction via the SMURF1-mediated ubiquitin-proteasome pathway. Both chemical inhibiting MAT2A using PGG and genetically ablating Mat2a trigger pyroptosis—a form of immunogenic cell death—in both macrophages and tumor cells by activating GSDME, resulting in an anti-tumor immune response effectively and suppressing tumor progression.
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Fudan University Press
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