The biological roles of Type I interferon: biological functions of IFIT-1 and a novel signaling pathway

[[abstract]]Interferon-(IFN), a cytokine with modulatory activities on many cell types, is useful for treating many types of cancer and infectious diseases. The common set of genes induced by virus infection, IFN, and dsRNA is called viral stress-inducible genes (VSIG). One of VSIG, P56 is the product of mRNA 561 encode by the ISG56 gene (also known as IFIT1). It contains six tetratricopeptide repeats (TPRs) spaced evenly along the entire protein, which are known to mediated protein-protein interactions. Previous studies we known that P56 can bind to the large eIF-3 complex that contains P48 subunit and to inhibit protein synthesis, which blocks the formation of stable eIF3‧ternary complex. With six TPRs, P56 may interact with various proteins and influence some other biological process. In our study, we found the ribosomal protein 15 (RPL15) interacted with p56 by phage display experiments in vitro. The p56-RPL15 interaction was confirmed by pull-down assay in vivo. Furthermore, we found to down-regulation of RPL15 expression or overexpression of p56 was inhibited cell growth and more sensitivity with IFN by MTT assay. Previous study indicated that induction of STAT6 complexes by IFNα appears to be cell type specific. STAT6 in response to IFNα is predominantly detected in B cells. It was first proved in our research that type I IFN can activate STAT6 in hepatoma cells and lead to the formation of stat2 : stat6 complexes. The STAT6 activation is mediated by the associating with activated STAT2 and it will result in the production of IL1-Ra