title: An RNAi screen identifies USP2 as a factor required for TNF-α-induced NF-κB signaling.
abstract: 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.
authors.affiliation: 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.
authors.forename: Marie
authors.initials: M
authors.lastname: Metzig
authors.forename: Dorothee
authors.initials: D
authors.lastname: Nickles
authors.forename: Christina
authors.initials: C
authors.lastname: Falschlehner
authors.forename: Judith
authors.initials: J
authors.lastname: Lehmann-Koch
authors.forename: Beate K
authors.initials: BK
authors.lastname: Straub
authors.forename: Wilfried
authors.initials: W
authors.lastname: Roth
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D010450:Endopeptidases / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D043222:Ubiquitin Thiolesterase
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase