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A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling
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Veröffentlicht in: | Molecular and cellular biology 32(2012), 17, Seite 3372-3381 |
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Personen und Körperschaften: | , , |
Titel: | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling/ Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros |
Format: | E-Book-Kapitel |
Sprache: | Englisch |
veröffentlicht: |
2012
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Gesamtaufnahme: |
: Molecular and cellular biology, 32(2012), 17, Seite 3372-3381
, volume:32 |
Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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520 | |a Tumor necrosis factor alpha (TNF-α) is a potent inflammatory cytokine secreted upon cellular stress as well as immunological stimuli and is implicated in the pathology of inflammatory diseases and cancer. The therapeutic potential of modifying TNF-α pathway activity has been realized in several diseases, and antagonists of TNF-α have reached clinical applications. While much progress in the understanding of signaling downstream of the TNF-α receptor complex has been made, the compendium of factors required for signal transduction is still not complete. In order to find novel regulators of proinflammatory signaling induced by TNF-α, we conducted a genome-wide small interfering RNA screen in human cells. We identified several new candidate modulators of TNF-α signaling, which were confirmed in independent experiments. Specifically, we show that caspase 4 is required for the induction of NF-κB activity, while it appears to be dispensable for the activation of the Jun N-terminal protein kinase signaling branch. Taken together, our experiments identify caspase 4 as a novel regulator of TNF-α-induced NF-κB signaling that is required for the activation of IκB kinase. We further provide the genome-wide RNA interference data set as a compendium in a format compliant with minimum information about an interfering RNA experiment (MAIRE). | ||
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author | Nickles, Dorothee, Oliver Metzig, Marie, Boutros, Michael |
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contents | Tumor necrosis factor alpha (TNF-α) is a potent inflammatory cytokine secreted upon cellular stress as well as immunological stimuli and is implicated in the pathology of inflammatory diseases and cancer. The therapeutic potential of modifying TNF-α pathway activity has been realized in several diseases, and antagonists of TNF-α have reached clinical applications. While much progress in the understanding of signaling downstream of the TNF-α receptor complex has been made, the compendium of factors required for signal transduction is still not complete. In order to find novel regulators of proinflammatory signaling induced by TNF-α, we conducted a genome-wide small interfering RNA screen in human cells. We identified several new candidate modulators of TNF-α signaling, which were confirmed in independent experiments. Specifically, we show that caspase 4 is required for the induction of NF-κB activity, while it appears to be dispensable for the activation of the Jun N-terminal protein kinase signaling branch. Taken together, our experiments identify caspase 4 as a novel regulator of TNF-α-induced NF-κB signaling that is required for the activation of IκB kinase. We further provide the genome-wide RNA interference data set as a compendium in a format compliant with minimum information about an interfering RNA experiment (MAIRE). |
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spelling | Nickles, Dorothee VerfasserIn (DE-588)140704043 (DE-627)620896299 (DE-576)319766888 aut, A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros, 2012, 10, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Published ahead of print 25 June 2012, Gesehen am 15.06.2018, Tumor necrosis factor alpha (TNF-α) is a potent inflammatory cytokine secreted upon cellular stress as well as immunological stimuli and is implicated in the pathology of inflammatory diseases and cancer. The therapeutic potential of modifying TNF-α pathway activity has been realized in several diseases, and antagonists of TNF-α have reached clinical applications. While much progress in the understanding of signaling downstream of the TNF-α receptor complex has been made, the compendium of factors required for signal transduction is still not complete. In order to find novel regulators of proinflammatory signaling induced by TNF-α, we conducted a genome-wide small interfering RNA screen in human cells. We identified several new candidate modulators of TNF-α signaling, which were confirmed in independent experiments. Specifically, we show that caspase 4 is required for the induction of NF-κB activity, while it appears to be dispensable for the activation of the Jun N-terminal protein kinase signaling branch. Taken together, our experiments identify caspase 4 as a novel regulator of TNF-α-induced NF-κB signaling that is required for the activation of IκB kinase. We further provide the genome-wide RNA interference data set as a compendium in a format compliant with minimum information about an interfering RNA experiment (MAIRE)., Oliver Metzig, Marie 1985- VerfasserIn (DE-588)1023029898 (DE-627)717349624 (DE-576)366289691 aut, Boutros, Michael VerfasserIn (DE-588)1023031132 (DE-627)717350045 (DE-576)366291831 aut, Enthalten in Molecular and cellular biology Washington, DC : Soc., 1981 32(2012), 17, Seite 3372-3381 Online-Ressource (DE-627)269533656 (DE-600)1474919-1 (DE-576)088704181 1098-5549 nnns, volume:32 year:2012 number:17 pages:3372-3381 extent:10, http://dx.doi.org/10.1128/MCB.06739-11 Verlag Resolving-System kostenfrei Volltext, http://mcb.asm.org/content/32/17/3372 Verlag kostenfrei Volltext, http://dx.doi.org/10.1128/MCB.06739-11 LFER, LFER 2018-07-10T00:00:00Z |
spellingShingle | Nickles, Dorothee, Oliver Metzig, Marie, Boutros, Michael, A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling, Tumor necrosis factor alpha (TNF-α) is a potent inflammatory cytokine secreted upon cellular stress as well as immunological stimuli and is implicated in the pathology of inflammatory diseases and cancer. The therapeutic potential of modifying TNF-α pathway activity has been realized in several diseases, and antagonists of TNF-α have reached clinical applications. While much progress in the understanding of signaling downstream of the TNF-α receptor complex has been made, the compendium of factors required for signal transduction is still not complete. In order to find novel regulators of proinflammatory signaling induced by TNF-α, we conducted a genome-wide small interfering RNA screen in human cells. We identified several new candidate modulators of TNF-α signaling, which were confirmed in independent experiments. Specifically, we show that caspase 4 is required for the induction of NF-κB activity, while it appears to be dispensable for the activation of the Jun N-terminal protein kinase signaling branch. Taken together, our experiments identify caspase 4 as a novel regulator of TNF-α-induced NF-κB signaling that is required for the activation of IκB kinase. We further provide the genome-wide RNA interference data set as a compendium in a format compliant with minimum information about an interfering RNA experiment (MAIRE). |
swb_id_str | 506408213 |
title | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling |
title_auth | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling |
title_full | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros |
title_fullStr | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros |
title_full_unstemmed | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros |
title_in_hierarchy | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling / Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros, |
title_short | A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling |
title_sort | genome wide rna interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling |
url | http://dx.doi.org/10.1128/MCB.06739-11, http://mcb.asm.org/content/32/17/3372 |