Granzyme B proteolyzes receptors important to proliferation and survival, tipping the balance toward apoptosis.
Granzyme B is critical to the ability of natural killer cells and cytotoxic T lymphocytes to induce efficient cell death of virally infected or tumor cell targets. Although granzyme B can cleave and activate caspases to induce apoptosis, granzyme B can also cause caspase-independent cell death. Thirteen prospective granzyme B ... substrates were identified from a cDNA expression-cleavage screen, including Hsp70, Notch1, fibroblast growth factor receptor-1 (FGFR1), poly-A-binding protein, cAbl, heterogeneous nuclear ribonucleoprotein H', Br140, and intersectin-1. Validation revealed that Notch1 is a substrate of both granzyme B and caspases, whereas FGFR1 is a caspase-independent substrate of granzyme B. Proteolysis of FGFR1 in prostate cancer cells has functionally relevant consequences that indicate its cleavage may be advantageous for granzyme B to kill prostate cancer cells. Therefore, granzyme B not only activates pro-death functions within a target, but also has a previously unidentified role in inactivating pro-growth signals to cause cell death.
Mesh Terms:
Amino Acid Sequence, Apoptosis, Caspases, Cell Line, Tumor, Cell Proliferation, Cell Survival, Gene Library, Granzymes, HSP70 Heat-Shock Proteins, Humans, Male, Molecular Sequence Data, Prostatic Neoplasms, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Notch1, Serine Endopeptidases
Amino Acid Sequence, Apoptosis, Caspases, Cell Line, Tumor, Cell Proliferation, Cell Survival, Gene Library, Granzymes, HSP70 Heat-Shock Proteins, Humans, Male, Molecular Sequence Data, Prostatic Neoplasms, Receptor, Fibroblast Growth Factor, Type 1, Receptor, Notch1, Serine Endopeptidases
J. Biol. Chem.
Date: Sep. 22, 2006
PubMed ID: 16798735
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