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The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics

The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics
The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics
Granzyme B, a serine protease derived from cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell granules, plays an important role in coordinating apoptosis of CTL and NK target cells. Here, we report that granzyme B targets the cytoskeleton by cleaving and removing the acidic C-terminal tail of alpha-tubulin. Consistent with this, Granzyme B markedly enhanced rates of microtubule polymerization in vitro, most likely by removal of an autoinhibitory domain within the tubulin C terminus. Moreover, delivery of Granzyme B into HeLa target cells promoted dramatic reorganization of the microtubule network in a caspase-independent manner. These data reveal that granzyme B directly attacks a major component of the cell cytoskeleton, which may contribute to the incapacitation of target cells during CTL/NK-mediated killing.
0021-9258
8118-8125
Adrain, Colin
f7950ceb-b788-4d86-a607-b9efc4437142
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Brumatti, Gabriela
87802265-47e9-47ad-b74e-1bb4410fc7cd
Delivani, Petrina
8840fdf6-c287-4dbf-837c-56a36b1e7e0e
Martin, Seamus J.
3df02649-5634-44da-834d-098937a7ae5b
Adrain, Colin
f7950ceb-b788-4d86-a607-b9efc4437142
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Brumatti, Gabriela
87802265-47e9-47ad-b74e-1bb4410fc7cd
Delivani, Petrina
8840fdf6-c287-4dbf-837c-56a36b1e7e0e
Martin, Seamus J.
3df02649-5634-44da-834d-098937a7ae5b

Adrain, Colin, Duriez, Patrick J., Brumatti, Gabriela, Delivani, Petrina and Martin, Seamus J. (2006) The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics. The Journal of Biological Chemistry, 281 (12), 8118-8125. (doi:10.1074/jbc.M509361200). (PMID:16415351)

Record type: Article

Abstract

Granzyme B, a serine protease derived from cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell granules, plays an important role in coordinating apoptosis of CTL and NK target cells. Here, we report that granzyme B targets the cytoskeleton by cleaving and removing the acidic C-terminal tail of alpha-tubulin. Consistent with this, Granzyme B markedly enhanced rates of microtubule polymerization in vitro, most likely by removal of an autoinhibitory domain within the tubulin C terminus. Moreover, delivery of Granzyme B into HeLa target cells promoted dramatic reorganization of the microtubule network in a caspase-independent manner. These data reveal that granzyme B directly attacks a major component of the cell cytoskeleton, which may contribute to the incapacitation of target cells during CTL/NK-mediated killing.

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Published date: 24 March 2006

Identifiers

Local EPrints ID: 164801
URI: http://eprints.soton.ac.uk/id/eprint/164801
ISSN: 0021-9258
PURE UUID: 8e0f2fbb-e234-4127-9714-7225e3cbb956

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Date deposited: 04 Oct 2010 13:51
Last modified: 16 Jul 2019 23:52

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