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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 |
Zusammenfassung: | 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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Beschreibung: |
Published ahead of print 25 June 2012 Gesehen am 15.06.2018 |
Umfang: | 10 |
ISSN: |
1098-5549
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DOI: | 10.1128/MCB.06739-11 |