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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
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A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in

Q Tian1, M Streuli, H Saito

  • 1Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

Cell
|November 1, 1991
PubMed

Insights

Cytolytic lymphocytes (CTLs) utilize TIA-1, a protein found in cytolytic granules, to induce apoptosis. Both natural and recombinant TIA-1 trigger DNA fragmentation, identifying it as a key molecule in cell-mediated cytotoxicity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cytolytic lymphocytes (CTLs) are crucial for adaptive immunity.
  • CTLs employ cytoplasmic granules containing effector molecules like perforin and serine proteases to eliminate target cells.
  • The specific granule components responsible for inducing target cell apoptosis remain incompletely understood.

Purpose of the Study:

  • To clone and functionally characterize two isoforms of a novel cytolytic granule protein, TIA-1.
  • To elucidate the structural relationship between TIA-1 isoforms and their potential role in apoptosis.

Main Methods:

  • cDNA cloning of TIA-1 isoforms.
  • Sequence analysis to determine protein structure and domains.
  • Functional assays using digitonin-permeabilized thymocytes to assess DNA fragmentation induction.

Main Results:

  • Two related TIA-1 isoforms, rp40-TIA-1 (40 kd) and a 15 kd isoform, were identified.
  • rp40-TIA-1 shares structural homology with poly(A)-binding proteins, featuring RNA-binding domains and a glutamine-rich domain.
  • The 15 kd TIA-1 isoform, prevalent in granules, is derived from rp40-TIA-1 via proteolytic processing.
  • Both natural and recombinant TIA-1 induced DNA fragmentation in thymocytes.

Conclusions:

  • TIA-1 isoforms are components of cytolytic granules.
  • TIA-1 possesses the ability to induce DNA fragmentation, a hallmark of apoptosis.
  • TIA-1 is likely a critical effector molecule responsible for inducing apoptosis in CTL targets.

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