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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-03, Vol.281 (12), p.8118-8125
Main Authors: Adrain, Colin, Duriez, Patrick J., Brumatti, Gabriela, Delivani, Petrina, Martin, Seamus J.
Format: Article
Language:English
Subjects:
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
Serine Endopeptidases - metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
T-Lymphocytes, Cytotoxic - metabolism
Time Factors
Transcription, Genetic
Tubulin - chemistry
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Summary: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 α-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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M509361200