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 dise...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
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| In: |
Molecular and cellular biology
Year: 2012, Volume: 32, Issue: 17, Pages: 3372-3381 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/MCB.06739-11 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1128/MCB.06739-11 Verlag, kostenfrei, Volltext: http://mcb.asm.org/content/32/17/3372 
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| Author Notes: | Dorothee Nickles, Christina Falschlehner, Marie Metzig, and Michael Boutros |
| Summary: | 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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| Item Description: | Published ahead of print 25 June 2012 Gesehen am 15.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/MCB.06739-11 |