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Int J Cancer. 2011 Aug 1;129(3):607-18. doi: 10.1002/ijc.26124.

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

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German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, and Department for Cell and Molecular Biology, Faculty for Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.


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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