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פותח על ידי קלירמאש פתרונות בע"מ -
Baculovirus apoptotic suppressor P49 is a substrate inhibitor of initiator caspases resistant to P35 in vivo
Year:
2002
Source of publication :
eLife
Authors :
צ'חנובסקי, נור
;
.
Volume :
21
Co-Authors:
Zoog, S.J., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Schiller, J.J., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Wetter, J.A., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Chejanovsky, N., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Friesen, P.D., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Facilitators :
From page:
5130
To page:
5140
(
Total pages:
11
)
Abstract:
Caspases play a critical role in the execution of metazoan apoptosis and are thus attractive therapeutic targets for apoptosis-associated diseases. Here we report that baculovirus P49, a homolog of pancaspase inhibitor P35, prevents apoptosis in invertebrates by inhibiting an initiator caspase that is P35 insensitive. Consequently P49 blocked proteolytic activation of effector caspases at a unique step upstream from that affected by P35 but downstream from inhibitor of apoptosis Op-IAP. Like P35, P49 was cleaved by and stably associated with its caspase target. Ectopically expressed P49 blocked apoptosis in cultured cells from a phylogenetically distinct organism, Drosophila melanogaster. Furthermore, P49 inhibited human caspase-9, demonstrating its capacity to affect a vertebrate initiator caspase. Thus, P49 is a substrate inhibitor with a novel in vivo specificity for a P35-insensitive initiator caspase that functions at an evolutionarily conserved step in the caspase cascade. These data indicate that activated initiator caspases provide another effective target for apoptotic intervention by substrate inhibitors.
Note:
Related Files :
animal cell
apoptosis
Baculoviridae
caspase 9
invertebrate
in vivo study
Melanogaster
protein p49
unclassified drug
Vertebrata
עוד תגיות
תוכן קשור
More details
DOI :
10.1093/emboj/\\|[ast
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
22128
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:49
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Scientific Publication
Baculovirus apoptotic suppressor P49 is a substrate inhibitor of initiator caspases resistant to P35 in vivo
21
Zoog, S.J., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Schiller, J.J., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Wetter, J.A., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Chejanovsky, N., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Friesen, P.D., Institute for Molecular Virology, R.M.Bock Laboratories, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706-1596, United States
Baculovirus apoptotic suppressor P49 is a substrate inhibitor of initiator caspases resistant to P35 in vivo
Caspases play a critical role in the execution of metazoan apoptosis and are thus attractive therapeutic targets for apoptosis-associated diseases. Here we report that baculovirus P49, a homolog of pancaspase inhibitor P35, prevents apoptosis in invertebrates by inhibiting an initiator caspase that is P35 insensitive. Consequently P49 blocked proteolytic activation of effector caspases at a unique step upstream from that affected by P35 but downstream from inhibitor of apoptosis Op-IAP. Like P35, P49 was cleaved by and stably associated with its caspase target. Ectopically expressed P49 blocked apoptosis in cultured cells from a phylogenetically distinct organism, Drosophila melanogaster. Furthermore, P49 inhibited human caspase-9, demonstrating its capacity to affect a vertebrate initiator caspase. Thus, P49 is a substrate inhibitor with a novel in vivo specificity for a P35-insensitive initiator caspase that functions at an evolutionarily conserved step in the caspase cascade. These data indicate that activated initiator caspases provide another effective target for apoptotic intervention by substrate inhibitors.
Scientific Publication
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