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An RNAi screen identifies USP2 as a factor required for TNF-α-induced NF-κB signaling

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Tumor necrosis factor α (TNF-α) signaling pathways play important roles during tumorigenesis and inflammation. Ubiquitin-dependent processes are central to the regulation of TNF-α and nuclear factor κB (NF-κB) signaling. We performed a targeted siRNA screen for ubiquitin-specific proteases (USPs) an...

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Hauptverfasser: Oliver Metzig, Marie (VerfasserIn) , Nickles, Dorothee (VerfasserIn) , Falschlehner, Christina (VerfasserIn) , Lehmann-Koch, Judith (VerfasserIn) , Straub, Beate Katharina (VerfasserIn) , Roth, Wilfried (VerfasserIn) , Boutros, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 07 April 2011
In: International journal of cancer
Year: 2011, Jahrgang: 129, Heft: 3, Pages: 607-618
ISSN:1097-0215
DOI:10.1002/ijc.26124
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ijc.26124
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.26124
Volltext
Verfasserangaben:Marie Metzig, Dorothee Nickles, Christina Falschlehner, Judith Lehmann-Koch, Beate K. Straub, Wilfried Roth and Michael Boutros
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Zusammenfassung:Tumor necrosis factor α (TNF-α) signaling pathways play important roles during tumorigenesis and inflammation. Ubiquitin-dependent processes are central to the regulation of TNF-α and nuclear factor κB (NF-κB) signaling. We performed a targeted siRNA screen for ubiquitin-specific proteases (USPs) and identified USP2 as a modulator of TNF-α-induced NF-κB signaling. We showed that USP2 is required for the phosphorylation of IκB, nuclear translocation of NF-κB and expression of NF-κB-dependent target genes and IL-8 secretion. Our study also provides evidence for isoform-specific functions of USP2. The immunohistochemical analysis of breast carcinomas revealed that USP2 expression is frequently downregulated. Together, our results implicate USP2 as a novel positive regulator of TNF-α-induced NF-κB signaling and show that its expression is altered in tumor cells.
Beschreibung:Gesehen am 19.08.2022
Beschreibung:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.26124

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