Abstract
Abstract CTL exocytosis of granules containing perforin and granzyme proteases induces apoptotic cell death. Either granzyme A or B can act with perforin to trigger apoptosis. Granzyme B activates a ubiquitous apoptotic cascade induced by caspase cleavage, but the granzyme A pathway is largely unknown. Using affinity chromatography with recombinant mutant inactive granzyme A, we previously isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein) I and II. PHAP II, a substrate of granzyme A, is degraded within minutes of CTL attack. Two additional cytoplasmic proteins of 27 and 53 kDa bind strongly to the mutant granzyme A column, requiring 6 M urea to elute. Sequencing identified these as the monomer and dimer of hsp27, a small heat shock protein up-regulated by stress and cellular activation. Hsp27 coprecipitates with granzyme A from cytoplasmic lysates and is not a substrate of the enzyme. Hsp27 translocates to the detergent-insoluble fraction of target cells and relocalizes from diffuse cytoplasmic staining to long filamentous fibers, especially concentrated in a perinuclear region, within minutes of CTL attack. Hsp27 may participate in morphologic changes during granule-mediated lysis. Low or absent levels of hsp27 expression in T lymphocytes, even after heat shock, may play a role in CTL resistance to granule-mediated lysis.
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Dates
Type | When |
---|---|
Created | 2 years, 7 months ago (Dec. 31, 2022, 7:15 p.m.) |
Deposited | 4 months, 3 weeks ago (March 31, 2025, 10 a.m.) |
Indexed | 4 months, 3 weeks ago (March 31, 2025, 10:40 a.m.) |
Issued | 27 years, 1 month ago (July 1, 1998) |
Published | 27 years, 1 month ago (July 1, 1998) |
Published Online | 27 years, 1 month ago (July 1, 1998) |
Published Print | 27 years, 1 month ago (July 1, 1998) |
@article{Beresford_1998, title={A Role for Heat Shock Protein 27 in CTL-Mediated Cell Death}, volume={161}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.161.1.161}, DOI={10.4049/jimmunol.161.1.161}, number={1}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Beresford, Paul J and Jaju, Madhuri and Friedman, Rachel S and Yoon, Margaret J and Lieberman, Judy}, year={1998}, month=jul, pages={161–167} }