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

Colin Adrain; Patrick J Duriez; Gabriela Brumatti; Petrina Delivani; Seamus J Martin

doi:10.1074/jbc.M509361200

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

Colin Adrain
, Patrick J Duriez
, Gabriela Brumatti
, Petrina Delivani
, Seamus J Martin

Research output: Contribution to journal › Article › peer-review

75 Citations (Scopus)

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.

Original language	English
Pages (from-to)	8118-25
Number of pages	8
Journal	The Journal of Biological Chemistry
Volume	281
Issue number	12
DOIs	https://doi.org/10.1074/jbc.M509361200
Publication status	Published - 24 Mar 2006
Externally published	Yes

Keywords

Amino Acid Motifs
Amino Acid Sequence
Apoptosis
Caspases/metabolism
Cell-Free System/metabolism
Cytoskeleton/metabolism
Electrophoresis, Gel, Two-Dimensional
Enzyme Activation
Granzymes
HeLa Cells
Humans
Jurkat Cells
Killer Cells, Natural/metabolism
Microtubules/metabolism
Mitosis
Molecular Sequence Data
Protein Biosynthesis
Protein Structure, Tertiary
RNA, Small Interfering/metabolism
Serine Endopeptidases/chemistry
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
T-Lymphocytes, Cytotoxic/metabolism
Time Factors
Transcription, Genetic
Tubulin/chemistry

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10.1074/jbc.M509361200

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

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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author = "Colin Adrain and Duriez, \{Patrick J\} and Gabriela Brumatti and Petrina Delivani and Martin, \{Seamus J\}",

year = "2006",

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doi = "10.1074/jbc.M509361200",

language = "English",

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journal = "The Journal of Biological Chemistry",

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TY - JOUR

T1 - The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics

AU - Adrain, Colin

AU - Duriez, Patrick J

AU - Brumatti, Gabriela

AU - Delivani, Petrina

AU - Martin, Seamus J

PY - 2006/3/24

Y1 - 2006/3/24

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Apoptosis

KW - Caspases/metabolism

KW - Cell-Free System/metabolism

KW - Cytoskeleton/metabolism

KW - Electrophoresis, Gel, Two-Dimensional

KW - Enzyme Activation

KW - Granzymes

KW - HeLa Cells

KW - Humans

KW - Jurkat Cells

KW - Killer Cells, Natural/metabolism

KW - Microtubules/metabolism

KW - Mitosis

KW - Molecular Sequence Data

KW - Protein Biosynthesis

KW - Protein Structure, Tertiary

KW - RNA, Small Interfering/metabolism

KW - Serine Endopeptidases/chemistry

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - T-Lymphocytes, Cytotoxic/metabolism

KW - Time Factors

KW - Transcription, Genetic

KW - Tubulin/chemistry

U2 - 10.1074/jbc.M509361200

DO - 10.1074/jbc.M509361200

M3 - Article

C2 - 16415351

SN - 0021-9258

VL - 281

SP - 8118

EP - 8125

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

IS - 12

ER -

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

Abstract

Keywords

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