An RNAi screen identifies USP2 as a factor required for TNF-alpha-induced NF-kappa B signaling

作者：Metzig Marie; Nickles Dorothee; Falschlehner Christina; Lehmann Koch Judith; Straub Beate K; Roth Wilfried; Boutros Michael^*

来源：International Journal of Cancer, 2011, 129(3): 607-618.

DOI：10.1002/ijc.26124

• RNAi
• signaling
• NF-kappa B
• functional genomics
• breast cancer

Tumor necrosis factor alpha (TNF-alpha) signaling pathways play important roles during tumorigenesis and inflammation. Ubiquitin-dependent processes are central to the regulation of TNF-alpha and nuclear factor kappa B (NF-kappa B) signaling. We performed a targeted siRNA screen for ubiquitin-specific proteases (USPs) and identified USP2 as a modulator of TNF-alpha-induced NF-kappa B signaling. We showed that USP2 is required for the phosphorylation of I kappa B, nuclear translocation of NF-kappa B and expression of NF-kappa B-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-alpha-induced NF-kappa B signaling and show that its expression is altered in tumor cells.

• 出版日期2011-8-1