Induction of rapid histone degradation by the cytotoxic T lymphocyte protease Granzyme A |
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Authors: | Zhang D Pasternack M S Beresford P J Wagner L Greenberg A H Lieberman J |
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Affiliation: | Center for Blood Research, Massachusetts General Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA. |
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Abstract: | The cytotoxic T lymphocyte protease granzyme A induces caspase-independent cell death in which DNA single-strand nicking is observed instead of oligonucleosomal fragmentation. Granzyme A is a specific tryptase that concentrates in the nucleus of targeted cells and synergistically enhances DNA fragmentation induced by the caspase activator granzyme B. Here we show that granzyme A treatment of isolated nuclei enhances DNA accessibility to exogenous endonucleases. In vitro and after cell loading with perforin, GrnA completely degrades histone H1 and cleaves core histones into approximately 16-kDa fragments. Histone digestion provides a mechanism for unfolding compacted chromatin and facilitating endogenous DNase access to DNA during T cell and natural killer cell granule-mediated apoptosis. |
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