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

摘要

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 kappaB (NF-kappaB) signaling. We performed a targeted siRNA screen for ubiquitin-specific proteases (USPs) and identified USP2 as a modulator of TNF-alpha-induced NF-kappaB signaling. We showed that USP2 is required for the phosphorylation of IkappaB, nuclear translocation of NF-kappaB and expression of NF-kappaB-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-kappaB signaling and show that its expression is altered in tumor cells.