granzyme a mediated apoptosis pathway
| PAG Title | granzyme a mediated apoptosis pathway |
| PAG ID | WAG000231 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | One mechanism used by cytotoxic T cells to kill tumor cells and virus-infected cells is the release of perforin and granzyme proteins. Perforin proteins form pores in the membranes of the attacked cell, allowing the entry of Granzyme A and Granzyme B. Granzyme B induces caspase activation and cleavage of factors like ICAD, releasing DFF40 to fragment D, one of the hallmarks of apoptotic cell death (see Apoptotic D Fragmentation and Tissue Homeostasis pathway and Caspase Cascade in Apoptosis pathway). Granzyme A is also an abundant granzyme released by cytotoxic T cells and is important in cytotoxic T cell induced apoptosis, activating caspase independent pathways. Once in a cell, Granzyme A activates D nicking by the recently identified Dse NM23-H1, a tumor suppressor gene product whose expression is reduced in transformed, metastatic cells. The previous identification of NM23-H1 as a tumor suppressor indicates that its Dse activity plays an important role in immune surveillance to prevent cancer through the induction of tumor cell apoptosis. The activation of NM23-H1 occurs indirectly, through the cleavage of proteins that inhibit NM23-H1 in the SET complex, which includes SET, Ape1, pp32 and HMG2. SET is a substrate for the Granzyme A protease, and SET cleavage relieves NM23-H1 inhibition to cause apoptotic D degradation. |
| Species | Homo sapiens |
| nCoCo Score | 682 |
| Base PAG ID | WAG000231 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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