An RNAi screen identifies USP2 as a factor required for TNF-α-induced NF-κB signaling
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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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
07 April 2011
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| In: |
International journal of cancer
Year: 2011, Volume: 129, Issue: 3, Pages: 607-618 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.26124 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ijc.26124 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.26124 
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| Author Notes: | Marie Metzig, Dorothee Nickles, Christina Falschlehner, Judith Lehmann-Koch, Beate K. Straub, Wilfried Roth and Michael Boutros |
| Summary: | 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. |
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| Item Description: | Gesehen am 19.08.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.26124 |