Granzyme M directly cleaves inhibitor of caspase-activated DNase (CAD) to unleash CAD leading to DNA fragmentation.
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.
Mesh Terms:
Apoptosis, Apoptosis Regulatory Proteins, Caspases, Cell Death, Cell Nucleus, DNA Fragmentation, DNA, Single-Stranded, Deoxyribonucleases, Enzyme Inhibitors, Granzymes, Humans, Hydrolysis, Jurkat Cells, Poly(ADP-ribose) Polymerases, Protein Transport, Proteins, Serine Endopeptidases, Signal Transduction, Transfection
Apoptosis, Apoptosis Regulatory Proteins, Caspases, Cell Death, Cell Nucleus, DNA Fragmentation, DNA, Single-Stranded, Deoxyribonucleases, Enzyme Inhibitors, Granzymes, Humans, Hydrolysis, Jurkat Cells, Poly(ADP-ribose) Polymerases, Protein Transport, Proteins, Serine Endopeptidases, Signal Transduction, Transfection
J. Immunol.
Date: Jul. 15, 2006
PubMed ID: 16818775
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