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An RNAi screen identifies USP2 as a factor required for TNF‐α‐induced NF‐κB signaling
Author(s) -
Metzig Marie,
Nickles Dorothee,
Falschlehner Christina,
LehmannKoch Judith,
Straub Beate K.,
Roth Wilfried,
Boutros Michael
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26124
Subject(s) - signal transduction , tumor necrosis factor alpha , iκbα , cancer research , nf κb , phosphorylation , iκb kinase , nfkb1 , carcinogenesis , rna interference , microbiology and biotechnology , biology , chemistry , transcription factor , immunology , biochemistry , gene , rna
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.