DOI: 10.1073/pnas.101329598. Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis

Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis

10.1073/pnas.101329598

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Cytotoxic T lymphocytes (CTL) induce apoptosis by engaging death receptors or by exocytosis of cytolytic granules containing granzyme (Gzm) proteases and perforin. The lamins, which maintain the structural integrity of the nuclear envelope, are cleaved by caspases during caspase-mediated apoptosis. Although death receptor engagement and GzmB activate caspases, CTL also induce apoptosis during caspase blockade. Both GzmA and GzmB directly and efficiently cleave laminBin vitro,in situin isolated nuclei and in cells loaded with perforin and Gzms, even in the presence of caspase inhibitors. LaminB is cleaved by GzmA at concentrations of 3 nM, but GzmB is 50 times less active. GzmA cuts laminB at R392; GzmB cuts at the caspase VEVD231 site. Characteristic laminB fragments generated by Gzm proteolysis also are observed during CTL lysis, even in the presence of caspase inhibitors or in cells overexpressing bcl-2. Lamins A/C are direct substrates of GzmA, but not GzmB. GzmA and GzmB therefore directly target critical caspase substrates in caspase-resistant cells.

Bibliography

Zhang, D., Beresford, P. J., Greenberg, A. H., & Lieberman, J. (2001). Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis. Proceedings of the National Academy of Sciences, 98(10), 5746â5751.

Authors 4

Dong Zhang (first)
Paul J. Beresford (additional)
Arnold H. Greenberg (additional)
Judy Lieberman (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	1 year, 7 months ago (Jan. 4, 2024, 12:12 a.m.)
Indexed	1 month, 1 week ago (July 23, 2025, 9:01 a.m.)
Issued	24 years, 3 months ago (May 1, 2001)
Published	24 years, 3 months ago (May 1, 2001)
Published Online	24 years, 3 months ago (May 1, 2001)
Published Print	24 years, 3 months ago (May 8, 2001)

Funders 0

None

BibTeX

@article{Zhang_2001, title={Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.101329598}, DOI={10.1073/pnas.101329598}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zhang, Dong and Beresford, Paul J. and Greenberg, Arnold H. and Lieberman, Judy}, year={2001}, month=may, pages={5746–5751} }

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