FUNCTIONAL-ANALYSIS OF THE HUMAN INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN GENE PROMOTER

The third component of the interleukin (IL) 2 receptor, gamma chain, i s essential not only for IL-2- but also for IL-4-, IL-7-, IL-9-, and I L-15-induced proliferation of lymphocytes. To elucidate the mechanisms by which the gamma chain is expressed, we have analyzed the promoter region of the gamma chain gene. The 633-base pair fragment upstream of the initiation codon showed the promoter activity in human hematopoie tic cell lines, Jurkat and THP-1, when linked to the luciferase gene. With a series of 5'-deletion mutants, the basal promoter activity was found in a fragment from nucleotide 80 to 58 upstream from the RNA sta rt site, including an Ets binding sequence, Treatment of cells with ei ther 12-O-tetradecanoylphorbol-13-acetate or phytohemagglutinin but no t forskolin induced transcription from the gamma chain gene promoter. A viral trans acting transcriptional activator, Tax, of human T-cell l eukemia virus type I elevated expression of the gamma chain gene. In c ontrast, IL-2 decreased transcription from the IL-2 receptor gamma cha in promoter. These results suggest that expression of the gamma chain is regulated at the transcription level by extracellular stimuli and m ay be implicated in immune response.