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 |
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Pages (from-to) | 8118-25 |
Number of pages | 8 |
Journal | The Journal of Biological Chemistry |
Volume | 281 |
Issue number | 12 |
DOIs | |
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