Characterization of the human interleukin-2 receptor beta-chain gene promoter: regulation of promoter activity by ets gene products.

Abstract

The interleukin-2 receptor (IL-2R) 1 chain (IL-2RPI) is an essential signaling component of high-and intermediate-affinity . Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human I,-2RI3 gene exhibited promoter activity. We have now further characterized the promoter and delineated cis-acting regulatory regions. The region downstream of -363 is critical for basal and phorbol myristate acetate-inducible IL-2R13 promoter activity and contains at least three enhancerlike regions. Among them, the -56 to -34 enhancer was the most potent and had high-level activity in two T-celi lines but not in nonlymphoid HeLaS3 and MG63 cells. This enhancer contains a GGAA Ets binding site which bound two Ets family proteins, Ets-1 and GA-binding protein in vitro. Mutation of the Ets motif strongly diminished both promoter and enhancer activities. We conclude that this Ets binding site plays a key role in regulating basal and phorbol myristate acetate-inducible IL-2R13 promoter activity and may also contribute to tissue-specific expression of the IL-2R13 gene. Antigen stimulation of T cells results in production of interleukin-2 (IL-2) and induction of high-affinity IL-2 receptor (IL-2R). The interaction of IL-2 with high-affinity IL-2Rinduces signals which result in T-cell proliferation (reviewed in references 25, 39, and 48). High-and/or intermediateaffinity IL-2Rs also play important roles in IL-2-induced cytolytic activity of T cells (38), natural killer cells (38,46), and neutrophils (9, 50) and in immunoglobulin production by B cells (29,48). Since high-affinity receptors contain a (26, 30), 1 (18,35,42,47), and -y (40, 41) chains, and intermediate-affinity receptors contain 13 and y chains, IL-2RP is an essential subunit of both classes of functional receptors.

Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2Rβ That Is Defective in HIV-Infected Patients

“…Many Akt substrates are transcription factors or are directly involved in the regulation of gene transcription (45). PI3K is required for expression of Ets in T cells (46), and Ets and Sp-1 transcription factors in other cells (47,48), which are important in IL-2R␤ gene regulation (49,50).…”

The Ets-1 transcription factor is required for complete pre-T cell receptor function and allelic exclusion at the T cell receptor β locus

“…Ets-1 and other Ets proteins participate into the transcriptional regulation of numerous genes whose products are critical for the development or the function of lymphoid cells (24)(25)(26)(27)(28)(29). Thus, inactivation of Ets-1 could lower or extinguish expression of genes whose products are components of the pre-TCR or are involved in pre-TCR function.…”

GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes

“…Many TATA-less RNA polymerase II promoters contain typical initiator elements, i.e., short conserved sequences that are bound by proteins of the transcriptional machinery. Some of these promoters, including the CD3, CD4, CD11c, CD18, CD72, IL-2R␤, TGF␤ RII, Ets-2, murine laminin B2, type IV collagenase, thymidylate synthetase, and cytochrome c oxidase subunit IV promoters possess Ets-like binding motifs near their transcriptional start sites, suggesting a new class of initiator elements (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Recently, two PEA3 motifs that are bound by GABP factors were shown to function as a minimal transcriptional initiator element when placed in front of a luciferase gene (46).…”