PMID- 3132714 OWN - NLM STAT- MEDLINE DCOM- 19880725 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 85 IP - 12 DP - 1988 Jun TI - Regulation of interleukin 2 receptor alpha subunit (Tac or CD25 antigen) gene expression: binding of inducible nuclear proteins to discrete promoter sequences correlates with transcriptional activation. PG - 4468-72 AB - Transfection of deleted forms of the human interleukin 2 receptor alpha subunit (IL-2R alpha; also called CD25 or Tac antigen) gene (IL2RA) promoter revealed a requirement for sequences 3' of base -317 for phytohemagglutinin- and phorbol 12-myristate 13-acetate (PMA)-induced promoter activation in CD4+ Jurkat T cells. In contrast, sequences 3' of base -271 were sufficient for promoter induction in CD4-/CD8- YT-1 T cells or Jurkat cells expressing the transactivator protein (tat-I) of human T-cell lymphotropic virus type I (HTLV-I). Gel retardation assays revealed that nuclear extracts from induced, but not uninduced, Jurkat and YT-1 cells mediated the formation of two specific DNA-protein complexes with oligonucleotides spanning the region of the IL2RA promoter from position -291 to -245, which contains two imperfect direct repeats (IDRs). Consistent with the different 5' sequence requirements for promoter activation in Jurkat and YT-1 cells, oligonucleotides corresponding to the region from -267 to -243 (downstream IDR and flanking region) formed only one complex with induced Jurkat extracts but two complexes with induced YT-1 extracts. Oligonucleotides containing the region of the IL2RA promoter from -293 to -270 (upstream IDR and flanking region) failed to bind protein in either cell type. In further support of the biological significance of these DNA-protein interactions, the IL2RA oligonucleotide from -291 to -245 proved to be sufficient in either orientation to confer PMA inducibility to the mitogen-insensitive thymidine kinase gene promoter in Jurkat cells. Together, these findings suggest that the interaction of inducible DNA binding proteins with the IL2RA promoter between bases -291 and -245 plays an important role in mitogen-induced changes in the transcriptional activity of this receptor gene. Furthermore, the requisite 5' sequences appear to differ in T cells depending upon the nature of the activation signal and perhaps the stage of cellular maturation. FAU - Lowenthal, J W AU - Lowenthal JW AD - Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham 27710. FAU - Bohnlein, E AU - Bohnlein E FAU - Ballard, D W AU - Ballard DW FAU - Greene, W C AU - Greene WC LA - eng PT - Journal Article PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Interleukin-2) RN - 0 (Nuclear Proteins) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Interleukin-2) SB - IM MH - Base Sequence MH - Chromosome Deletion MH - *Gene Expression Regulation MH - *Genes MH - Genetic Vectors MH - Humans MH - Interleukin-2/*immunology MH - Molecular Sequence Data MH - Nuclear Proteins/metabolism MH - Promoter Regions, Genetic MH - Receptors, Immunologic/*genetics MH - Receptors, Interleukin-2 MH - *Transcription, Genetic PMC - PMC280451 EDAT- 1988/06/01 00:00 MHDA- 1988/06/01 00:01 PMCR- 1988/12/01 CRDT- 1988/06/01 00:00 PHST- 1988/06/01 00:00 [pubmed] PHST- 1988/06/01 00:01 [medline] PHST- 1988/06/01 00:00 [entrez] PHST- 1988/12/01 00:00 [pmc-release] AID - 10.1073/pnas.85.12.4468 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1988 Jun;85(12):4468-72. doi: 10.1073/pnas.85.12.4468.