Abstract
Granzyme (Gzm)M is constitutively highly expressed in NK cells that may play a critical role in NK cell-mediated cytolysis. However, the function of GzmM has been less defined. Just one report showed GzmM induces a caspase-independent death pathway. In this study, we demonstrate a protein transfection reagent Pro-Ject can efficiently transport GzmM into target cells. GzmM initiates caspase-dependent apoptosis with typical apoptotic nuclear morphology. GzmM induces DNA fragmentation, not DNA nicking. GzmM can directly degrade inhibitor of caspase-activated DNase to release the nuclease activity of caspase-activated DNase for damaging DNA. Furthermore, GzmM cleaves the DNA damage sensor enzyme poly(ADP-ribose) polymerase to prevent cellular DNA repair and force apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / genetics
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Apoptosis / immunology
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Apoptosis Regulatory Proteins
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Caspases / physiology
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Cell Death / genetics
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Cell Death / immunology
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Cell Nucleus / enzymology
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Cell Nucleus / genetics
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DNA Fragmentation* / genetics
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DNA Fragmentation* / immunology
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DNA, Single-Stranded / metabolism
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Deoxyribonucleases / metabolism*
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Enzyme Inhibitors / metabolism*
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Granzymes
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Humans
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Hydrolysis
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Jurkat Cells
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Transport / genetics
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Protein Transport / immunology
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Proteins / metabolism*
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism
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Serine Endopeptidases / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology
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Transfection
Substances
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Apoptosis Regulatory Proteins
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DNA, Single-Stranded
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Enzyme Inhibitors
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Proteins
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caspase-activated DNase inhibitor
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Poly(ADP-ribose) Polymerases
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Deoxyribonucleases
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caspase-activated deoxyribonuclease
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GZMM protein, human
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Granzymes
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Serine Endopeptidases
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Caspases