The 58-kilodalton inhibitor of the interferon-induced double-stranded RNA-activated protein kinase is a tetratricopeptide repeat protein with oncogenic properties.

摘要: The interferon-induced RNA-dependent protein kinase (PKR) is considered to play an important role in the cellular defense against viral infection and, addition, has been suggested be a tumor suppressor gene because of its growth-suppressive properties. Activation PKR by double-stranded RNAs leads phosphorylation alpha subunit eukaryotic initiation factor 2 (eIF-2 alpha) and resultant block synthesis initiation. To avoid consequences activation, many viruses have developed strategies down-regulate PKR. Recently, we reported on purification characterization inhibitor (referred as p58), which activated during influenza virus infection. Subsequent cloning sequencing revealed that p58 member tetratricopeptide repeat (TPR) family proteins. further examine physiological this inhibitor, stably transfected NIH 3T3 cells with expression plasmid containing cDNA under control cytomegalovirus early promoter. By taking advantage recently characterized species-specific monoclonal antibody, isolated cell lines overexpressed p58. These exhibited transformed phenotype, growing at faster rates higher saturation densities exhibiting anchorage-independent growth. Most importantly, inoculation nude mice p58-overexpressing gave rise production tumors. Finally, murine activity endogenous levels eIF-2 were reduced p58-expressing compared cells. data, taken together, suggest functions oncogene one mechanism induces malignant transformation through down-regulation subsequent deregulation synthesis.