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  Granzyme B-induced and Caspase 3-dependent Cleavage of Gelsolin by Mouse Cytotoxic T Cells Modifies Cytoskeleton Dynamics

Martin, P., Pardo, J., Schill, N., Jöckel, L., Berg, M., Froehlich, C. J., et al. (2010). Granzyme B-induced and Caspase 3-dependent Cleavage of Gelsolin by Mouse Cytotoxic T Cells Modifies Cytoskeleton Dynamics. The Journal of Biological Chemistry, 285, 18918-18927.

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 Creators:
Martin, Praxedis1, Author              
Pardo, Julián2, Author
Schill, Natalie3, Author              
Jöckel, Lars2, Author
Berg, Matthias, Author
Froehlich, Christopher J., Author
Wallich, Reinhard, Author
Simon, Markus M.3, Author              
Affiliations:
1Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243649              
2Max Planck Society, ou_persistent13              
3Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243654              

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 Abstract: Granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic T lymphocytes (Tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. Based on the notion that many gzms, including A, B, C, K, H, and M exhibit cytotoxic activity in vitro, all gzms are believed to serve a similar function in vivo. However, more recent evidence supports the concept that gzms are not unidimensional but, rather, possess non-cytotoxic potential, including stimulation of pro-inflammatory cytokines and anti-viral activities. The present study shows that isolated mouse gzmB cleaves the actin-severing mouse protein, cytoplasmic gelsolin (c-gelsolin) in vitro. However, when delivered to intact target cells by ex vivo immune Tc cells, gzmB mediates c-gelsolin proteolysis via activation of caspases 3/7. The NH(2)-terminal c-gelsolin fragment generated by either gzmB or caspase 3 in vitro constitutively severs actin filaments without destroying the target cells. The observation that gzmB secreted by Tc cells initiates a caspase cascade that disintegrates the actin cytoskeleton in target cells suggests that this intracellular process may contribute to anti-viral host defense.

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Language(s): eng - English
 Dates: 2010-06-11
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 529901
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Title: The Journal of Biological Chemistry
  Alternative Title : J. Biol. Chem.
Source Genre: Journal
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Pages: - Volume / Issue: 285 Sequence Number: - Start / End Page: 18918 - 18927 Identifier: -