scholarly journals The Exonuclease TREX1 Is in the SET Complex and Acts in Concert with NM23-H1 to Degrade DNA during Granzyme A-Mediated Cell Death

2006 ◽  
Vol 23 (1) ◽  
pp. 133-142 ◽  
Author(s):  
Dipanjan Chowdhury ◽  
Paul J. Beresford ◽  
Pengcheng Zhu ◽  
Dong Zhang ◽  
Jung-Suk Sung ◽  
...  
Keyword(s):  
Cell Death ◽  
Granzyme A ◽  
Exonuclease Trex1

scholarly journals Detection of active Granzyme A in NK92 cells with fluorescent activity-based probe

2019 ◽  
Author(s):  
Sonia Kołt ◽  
Tomasz Janiszewski ◽  
Dion Kaiserman ◽  
Sylwia Modrzycka ◽  
Scott J. Snipas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytotoxic T Lymphocytes ◽  
Serine Proteases ◽  
Effector Cell ◽  
Viral Infections ◽  
Cell Types ◽  
Substrate Specificities ◽  
Multiple Strategies ◽  
Granzyme A ◽  
Wide Range

AbstractCytotoxic T-lymphocytes (CTLs) and natural killer cells (NKs) kill compromised cells to defend against tumor and viral infections. Both effector cell types use multiple strategies to induce target cell death including Fas/CD95 activation; and the release of perforin and a group of lymphocyte granule serine proteases called granzymes. Granzymes have relatively broad and overlapping substrate specificities and may hydrolyze a wide range of peptidic epitopes; it is therefore challenging to identify their natural and synthetic substrates and to distinguish their localization and functions. Here, we present a specific and potent substrate, an inhibitor, and an activity-based probe of Granzyme A (GrA) that can be used to follow functional GrA in cells.

Histone H3 is Digested by Granzyme A During Compromised Cell Death in the Raji Cells

2015 ◽  
Vol 25 (9) ◽  
pp. 1578-1582 ◽  
Author(s):  
Phil Young Lee ◽  
Byoung Chul Park ◽  
Seung Wook Chi ◽  
Kwang-Hee Bae ◽  
Sunhong Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Histone H3 ◽  
Raji Cells ◽  
Granzyme A

scholarly journals Granzyme A Cleaves a Mitochondrial Complex I Protein to Initiate Caspase-Independent Cell Death

Cell ◽  
2008 ◽  
Vol 133 (4) ◽  
pp. 681-692 ◽  
Author(s):  
Denis Martinvalet ◽  
Derek M. Dykxhoorn ◽  
Roger Ferrini ◽  
Judy Lieberman
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Granzyme A

scholarly journals HMG2 Interacts with the Nucleosome Assembly Protein SET and Is a Target of the Cytotoxic T-Lymphocyte Protease Granzyme A

2002 ◽  
Vol 22 (8) ◽  
pp. 2810-2820 ◽  
Author(s):  
Zusen Fan ◽  
Paul J. Beresford ◽  
Dong Zhang ◽  
Judy Lieberman
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Dna Repair ◽  
Dna Binding ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Nucleosome Assembly ◽  
Nucleosome Assembly Protein ◽  
Granzyme A ◽  
Dna Binding And Bending

ABSTRACT The cytotoxic T-lymphocyte protease granzyme A induces caspase-independent cell death in which DNA single-stranded nicking is observed instead of oligonucleosomal fragmentation. A 270- to 420-kDa endoplasmic reticulum-associated complex (SET complex) containing the nucleosome assembly protein SET, the tumor suppressor pp32, and the base excision repair enzyme APE can induce single-stranded DNA damage in isolated nuclei in a granzyme A-dependent manner. The normal functions of the SET complex are unknown, but the functions of its components suggest that it is involved in activating transcription and DNA repair. We now find that the SET complex contains DNA binding and bending activities mediated by the chromatin-associated protein HMG2. HMG2 facilitates assembly of nucleoprotein higher-order structures by bending and looping DNA or by stabilizing underwound DNA. HMG2 is in the SET complex and coprecipitates with SET. By confocal microscopy, it is observed that cytoplasmic HMG2 colocalizes with SET in association with the endoplasmic reticulum, but most nuclear HMG2 is unassociated with SET. This physical association suggests that HMG2 may facilitate the nucleosome assembly, transcriptional activation, and DNA repair functions of SET and/or APE. HMG2, like SET and APE, is a physiologically relevant granzyme A substrate in targeted cells. HMG1, however, is not a substrate. Granzyme A cleavage after Lys65 in the midst of HMG box A destroys HMG2-mediated DNA binding and bending functions. Granzyme A cleavage and functional disruption of key nuclear substrates, including HMG2, SET, APE, lamins, and histones, are likely to cripple the cellular repair response to promote cell death in this novel caspase-independent death pathway.

scholarly journals The cytotoxic T lymphocyte protease granzyme A cleaves and inactivates poly(adenosine 5′-diphosphate-ribose) polymerase-1

Blood ◽  
2009 ◽  
Vol 114 (6) ◽  
pp. 1205-1216 ◽  
Author(s):  
Pengcheng Zhu ◽  
Denis Martinvalet ◽  
Dipanjan Chowdhury ◽  
Dong Zhang ◽  
Ann Schlesinger ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
T Lymphocyte ◽  
Catalytic Domain ◽  
Cytotoxic T Lymphocyte ◽  
Dominant Negative ◽  
Dna Binding Domain ◽  
Granzyme A ◽  
Dying Cells ◽  
Parp 1

Abstract Granzyme A (GzmA) in killer cells induces caspase-independent programmed cell death. In this study, we show that GzmA cleaves the DNA damage sensor poly(adenosine 5′-diphosphate-ribose) polymerase-1 (PARP-1) after Lys498 in its automodification domain, separating the DNA binding domain from the catalytic domain, which interferes with repair of GzmA-induced DNA damage and enhances susceptibility to GzmA-mediated death. Overexpressing K498A PARP-1 reduces GzmA-mediated death and drives dying cells to necrosis rather than apoptosis. Conversely, inhibiting or genetically disrupting PARP-1 enhances cell vulnerability. The N-terminal GzmA cleavage fragment of PARP-1 acts as a PARP-1 dominant negative, binding to DNA and blocking DNA repair. Disrupting PARP-1, which is also a caspase target, is therefore required for efficient apoptosis by both caspase-independent and caspase-dependent pathways.

Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A

10.1038/ni885 ◽  
2003 ◽  
Vol 4 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Zusen Fan ◽  
Paul J. Beresford ◽  
Dong Zhang ◽  
Zhan Xu ◽  
Carl D. Novina ◽  
...  
Keyword(s):  
Cell Death ◽  
Granzyme A ◽  
Repair Protein

scholarly journals Response: Granzyme A: cell death–inducing protease, proinflammatory agent, or both?

Blood ◽  
2009 ◽  
Vol 114 (18) ◽  
pp. 3969-3970 ◽  
Author(s):  
Denis Martinvalet ◽  
Michael Walch ◽  
Danielle K. Jensen ◽  
Jerome Thiery ◽  
Judy Lieberman
Keyword(s):  
Cell Death ◽  
Granzyme A ◽  
A Cell

A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus

2007 ◽  
Vol 85 (5) ◽  
pp. 531-537 ◽  
Author(s):  
Min Ae Lee-Kirsch ◽  
Dipanjan Chowdhury ◽  
Scott Harvey ◽  
Maoliang Gong ◽  
Lydia Senenko ◽  
...  
Keyword(s):  
Cell Death ◽  
Granzyme A ◽  
Familial Chilblain Lupus ◽  
Chilblain Lupus
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