CHARACTERIZATION OF THE HUMAN INTERLEUKIN-2 RECEPTOR BETA-CHAIN GENE PROMOTER - REGULATION OF PROMOTER ACTIVITY BY ETS GENE-PRODUCTS

The interleukin-2 receptor (IL-2R) beta chain (IL-2Rbeta) is an essent ial signaling component of high- and intermediate-affinity IL-2Rs. Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human IL-2Rbeta gene exhibited promoter activity. We have now further characterized the promoter and delineat ed cis-acting regulatory regions. The region downstream of -363 is cri tical for basal and phorbol myristate acetate-inducible IL-2Rbeta prom oter activity and contains at least three enhancer-like regions. Among them, the -56 to -34 enhancer was the most potent and had high-level activity in two T-cell lines but not in nonlymphoid HeLaS3 and MG63 ce lls. This enhancer contains a GGAA Ets binding site which bound two Et s family proteins, Ets-1 and GA-binding protein in vitro. Mutation of the Ets motif strongly diminished both promoter and enhancer activitie s. We conclude that this Ets binding site plays a key role in regulati ng basal and phorbol myristate acetate-inducible IL-2Rbeta promoter ac tivity and may also contribute to tissue-specific expression of the IL -2Rbeta gene.