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 journalArticle

66 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 languageEnglish
Pages (from-to)8118-25
Number of pages8
JournalThe Journal of biological chemistry
Volume281
Issue number12
DOIs
Publication statusPublished - 24 Mar 2006
Externally publishedYes

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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