THE EFFECT OF IL-2 TREATMENT ON TRANSCRIPTIONAL ATTENUATION IN PROTOONCOGENES PIM-1 AND C-MYB IN HUMAN THYMIC BLAST CELLS

IL-2 is the major mitogenic cytokine for mature human T cells. This gr owth factor has been shown previously to induce the expression of a nu mber of genes, including structural proteins, proto-oncogenes, and met abolic enzymes. Multiple mechanisms, including increases in mRNA stabi lity, protein synthesis, and new transcriptional initiation, have been studied to determine how IL-2 induces such a wide variety of genes. T he following studies show that a release of transcriptional attenuatio n is important in IL-2-induced gene expression. A thymic blast cell sy stem was developed and used to demonstrate that IL-2-deprived cells ha ve a marked attenuation of transcription in the 3' ends of the pim-1 a nd c-myb genes. IL-2 stimulation removes this attenuation and leads to read-through transcription. This effect is gene-specific, as demonstr ated by the fact that GAPDH is not attenuated in unstimulated cells. T he IL-2-mediated relief of attenuation occurs within 1 h of IL-2 stimu lation and is insensitive to the translation inhibitor cycloheximide, suggesting that new protein synthesis is not necessary. Further, the e ffect is insensitive to the immunosuppressant cyclosporin A, but is se nsitive to rapamycin and the tyrosine kinase inhibitor genistein. Thes e studies demonstrate that release of transcription attenuation is a m echanism used to induce gene expression in response to IL-2 treatment.