The Experts below are selected from a list of 32877 Experts worldwide ranked by ideXlab platform
Shashi Gujar - One of the best experts on this subject based on the ideXlab platform.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
Oncogene, 2016Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Reovirus is a naturally oncolytic virus that preferentially replicates in Ras-transformed cells and is currently undergoing clinical trials as a cancer therapeutic. Ras transformation Promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, and virus release through Apoptosis; however, the mechanism behind the latter is not well understood. Here, we show that reovirus alters the intracellular location of oncogenic Ras to induce Apoptosis of H-RasV12-transformed fibroblasts. Reovirus infection decreases Ras palmitoylation levels and causes accumulation of Ras in the Golgi through Golgi fragmentation. With the Golgi being the site of Ras palmitoylation, treatment of target cells with the palmitoylation inhibitor, 2-bromopalmitate (2BP), prompts a greater accumulation of H-RasV12 in the Golgi, and a dose-dependent increase in progeny virus release and subsequent spread. Conversely, tethering H-RasV12 to the plasma membrane (thereby preventing its movement to the Golgi) allows for efficient virus production, but results in basal levels of reovirus-induced cell death. Analysis of Ras downstream signaling reveals that cells expressing cycling H-RasV12 have elevated levels of phosphorylated JNK (c-Jun N-terminal kinase), and that Ras retained at the Golgi body by 2BP increases activation of the MEKK1/MKK4/JNK signaling pathway to Promote cell death. Collectively, our data suggest that reovirus induces Golgi fragmentation of target cells, and the subsequent accumulation of oncogenic Ras in the Golgi body initiates apoptotic signaling events required for virus release and spread.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release.
Oncogene, 2015Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
Thomas Langer - One of the best experts on this subject based on the ideXlab platform.
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PARL mediates Smac proteolytic maturation in mitochondria to Promote Apoptosis
Nature Cell Biology, 2017Co-Authors: Shotaro Saita, Hendrik Nolte, Kai Uwe Fiedler, Hamid Kashkar, A. Saskia Venne, René P. Zahedi, Marcus Krüger, Thomas LangerAbstract:Saita et al . show that PARL cleaves Smac (also known as DIABLO) to generate an IAP-binding motif required for its apoptotic activity, identifying PARL-mediated Smac processing as a pro-apoptotic mitochondrial pathway. Mitochondria drive Apoptosis by releasing pro-apoptotic proteins that Promote caspase activation in the cytosol. The rhomboid protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and plays an ill-defined role in Apoptosis. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) as a PARL substrate. In apoptotic cells, Smac is released into the cytosol and Promotes caspase activity by inhibiting inhibitors of Apoptosis (IAPs). Intramembrane cleavage of Smac by PARL generates an amino-terminal IAP-binding motif, which is required for its apoptotic activity. Loss of PARL impairs proteolytic maturation of Smac, which fails to bind XIAP. Smac peptidomimetics, downregulation of XIAP or cytosolic expression of cleaved Smac restores Apoptosis in PARL-deficient cells. Our results reveal a pro-apoptotic function of PARL and identify PARL-mediated Smac processing and cytochrome c release facilitated by OPA1-dependent cristae remodelling as two independent pro-apoptotic pathways in mitochondria.
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parl mediates smac proteolytic maturation in mitochondria to Promote Apoptosis
Nature Cell Biology, 2017Co-Authors: Shotaro Saita, Hendrik Nolte, Kai Uwe Fiedler, Hamid Kashkar, René P. Zahedi, Marcus Krüger, Saskia A Venne, Thomas LangerAbstract:Saita et al. show that PARL cleaves Smac (also known as DIABLO) to generate an IAP-binding motif required for its apoptotic activity, identifying PARL-mediated Smac processing as a pro-apoptotic mitochondrial pathway.
Katy A. Garant - One of the best experts on this subject based on the ideXlab platform.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
Oncogene, 2016Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Reovirus is a naturally oncolytic virus that preferentially replicates in Ras-transformed cells and is currently undergoing clinical trials as a cancer therapeutic. Ras transformation Promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, and virus release through Apoptosis; however, the mechanism behind the latter is not well understood. Here, we show that reovirus alters the intracellular location of oncogenic Ras to induce Apoptosis of H-RasV12-transformed fibroblasts. Reovirus infection decreases Ras palmitoylation levels and causes accumulation of Ras in the Golgi through Golgi fragmentation. With the Golgi being the site of Ras palmitoylation, treatment of target cells with the palmitoylation inhibitor, 2-bromopalmitate (2BP), prompts a greater accumulation of H-RasV12 in the Golgi, and a dose-dependent increase in progeny virus release and subsequent spread. Conversely, tethering H-RasV12 to the plasma membrane (thereby preventing its movement to the Golgi) allows for efficient virus production, but results in basal levels of reovirus-induced cell death. Analysis of Ras downstream signaling reveals that cells expressing cycling H-RasV12 have elevated levels of phosphorylated JNK (c-Jun N-terminal kinase), and that Ras retained at the Golgi body by 2BP increases activation of the MEKK1/MKK4/JNK signaling pathway to Promote cell death. Collectively, our data suggest that reovirus induces Golgi fragmentation of target cells, and the subsequent accumulation of oncogenic Ras in the Golgi body initiates apoptotic signaling events required for virus release and spread.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release.
Oncogene, 2015Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
Rémi M. Daigle - One of the best experts on this subject based on the ideXlab platform.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
Oncogene, 2016Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Reovirus is a naturally oncolytic virus that preferentially replicates in Ras-transformed cells and is currently undergoing clinical trials as a cancer therapeutic. Ras transformation Promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, and virus release through Apoptosis; however, the mechanism behind the latter is not well understood. Here, we show that reovirus alters the intracellular location of oncogenic Ras to induce Apoptosis of H-RasV12-transformed fibroblasts. Reovirus infection decreases Ras palmitoylation levels and causes accumulation of Ras in the Golgi through Golgi fragmentation. With the Golgi being the site of Ras palmitoylation, treatment of target cells with the palmitoylation inhibitor, 2-bromopalmitate (2BP), prompts a greater accumulation of H-RasV12 in the Golgi, and a dose-dependent increase in progeny virus release and subsequent spread. Conversely, tethering H-RasV12 to the plasma membrane (thereby preventing its movement to the Golgi) allows for efficient virus production, but results in basal levels of reovirus-induced cell death. Analysis of Ras downstream signaling reveals that cells expressing cycling H-RasV12 have elevated levels of phosphorylated JNK (c-Jun N-terminal kinase), and that Ras retained at the Golgi body by 2BP increases activation of the MEKK1/MKK4/JNK signaling pathway to Promote cell death. Collectively, our data suggest that reovirus induces Golgi fragmentation of target cells, and the subsequent accumulation of oncogenic Ras in the Golgi body initiates apoptotic signaling events required for virus release and spread.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release.
Oncogene, 2015Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
M Shmulevitz - One of the best experts on this subject based on the ideXlab platform.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
Oncogene, 2016Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Reovirus is a naturally oncolytic virus that preferentially replicates in Ras-transformed cells and is currently undergoing clinical trials as a cancer therapeutic. Ras transformation Promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, and virus release through Apoptosis; however, the mechanism behind the latter is not well understood. Here, we show that reovirus alters the intracellular location of oncogenic Ras to induce Apoptosis of H-RasV12-transformed fibroblasts. Reovirus infection decreases Ras palmitoylation levels and causes accumulation of Ras in the Golgi through Golgi fragmentation. With the Golgi being the site of Ras palmitoylation, treatment of target cells with the palmitoylation inhibitor, 2-bromopalmitate (2BP), prompts a greater accumulation of H-RasV12 in the Golgi, and a dose-dependent increase in progeny virus release and subsequent spread. Conversely, tethering H-RasV12 to the plasma membrane (thereby preventing its movement to the Golgi) allows for efficient virus production, but results in basal levels of reovirus-induced cell death. Analysis of Ras downstream signaling reveals that cells expressing cycling H-RasV12 have elevated levels of phosphorylated JNK (c-Jun N-terminal kinase), and that Ras retained at the Golgi body by 2BP increases activation of the MEKK1/MKK4/JNK signaling pathway to Promote cell death. Collectively, our data suggest that reovirus induces Golgi fragmentation of target cells, and the subsequent accumulation of oncogenic Ras in the Golgi body initiates apoptotic signaling events required for virus release and spread.
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Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release.
Oncogene, 2015Co-Authors: Katy A. Garant, M Shmulevitz, Rémi M. Daigle, Shashi GujarAbstract:Oncolytic reovirus induces intracellular redistribution of Ras to Promote Apoptosis and progeny virus release
