Activation of the interleukin-2 receptor alpha gene: regulatory role for DNA-protein interactions flanking the kappa B enhancer.

The human interleukin-2 receptor alpha (IL2R alpha) gene is transcriptionally activated by both phorbol esters and the HTLV-I trans-activator (Tax) protein through a mechanism that involves the interaction of inducible DNA binding proteins with a kappa B-like enhancer element (-267 to -256). Using mutated IL2R alpha promoter constructs in transient transfection and DNA binding assays, we now demonstrate that sequences located immediately upstream and downstream of the kappa B enhancer also contribute to the regulation of IL2R alpha gene expression. One upstream sequence termed UE-1 is preferentially required for phorbol ester relative to Tax-induced activation and specifically interacts with a constitutively expressed 56-kD cellular factor. In contrast, two overlapping downstream elements between nucleotides -252 and -239 appear to be required for both phorbol ester and Tax-induced activation. One of these elements, an Sp1-like sequence, binds a constitutively expressed 100-kD T-cell protein consistent in size with Sp1 isolated from HeLa cells. The second element, located between the kappa B and Sp1 sites, resembles the decanucleotide core of the serum response element (SRE) from the c-fos gene and interacts with a constitutively expressed factor. Together, these findings implicate a functional role for multiple constitutively expressed DNA binding proteins, in addition to the inducible kappa B-specific factors, in the overall regulation of IL2R alpha gene activation.