A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling

• Verfasst von: Nickles, Dorothee [VerfasserIn]
• Verfasst von: Oliver Metzig, Marie [VerfasserIn]
• Verfasst von: Boutros, Michael [VerfasserIn]
• Titel: A genome-wide RNA interference screen identifies caspase 4 as a factor required for tumor necrosis factor alpha signaling
• Verf.angabe: Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros
• Jahr: 2012
• Umfang: 10 S.
• Fussnoten: Published ahead of print 25 June 2012 ; Gesehen am 15.06.2018
• Titel Quelle: Enthalten in: Molecular and cellular biology
• Ort Quelle: London : Taylor & Francis, 1981
• Jahr Quelle: 2012
• Band/Heft Quelle: 32(2012), 17, Seite 3372-3381
• ISSN Quelle: 1098-5549
• DOI: doi:10.1128/MCB.06739-11
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1576408213

Abstract

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).