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
J. Biol. Chem.
Date: Sep. 22, 2006
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