Control of specificity and magnitude of NF-κB and STAT1-mediated gene activation through PIASy and PIAS1 cooperation

摘要: NF-κB and STATs regulate multiple cellular processes through the transcriptional activation of genes with diversified functions. Although molecular mechanisms that can turn on/off overall NF-κB/STAT signaling have been extensively studied, how NF-κB/STAT-target be differentially regulated is poorly understood. Here we report PIASy, a member PIAS (for protein inhibitor activated STAT) family, physiologically important repressor STAT1. Piasy deletion in dendritic cells resulted enhanced expression subset STAT1-dependent response to LPS or IFN-γ treatment, respectively. Consistently, null mice are hypersensitive LPS-induced endotoxic shock. Furthermore, PIASy PIAS1 display specific as well redundant effects on regulation NF-κB/STAT1 signaling. Pias1−/−Piasy−/− embryos died before day 11.5. The disruption one allele Pias1 Piasy−/− background significantly effect induction NF-κB/STAT1-dependent genes, vice versa. Our results demonstrate cooperates specificity magnitude NF-κB/STAT1-mediated gene activation.