The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites

被引:77
作者
Lin, JX [1 ]
Leonard, WJ [1 ]
机构
[1] NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892
关键词
D O I
10.1128/MCB.17.7.3714
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The interleukin-2 IL-2 receptor beta-chain (IL-2R beta) is an essential component of the receptors for IL-2 and IL-15, Although IL-2R beta is constitutively expressed by lymphocytes, its expression can be further induced by a number of stimuli, including phorbol 12-myristate 13-acetate (PMA). We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2R beta promoter. Both Sp1 and Sp3 bound to the 5'portion of this region, whereas a PMA-inducible factor (PIF) mainly bound to its 3'portion and bound to the Sp binding motifs as well, In Jurkat T cells, induction of PIF DNA binding activity was rapidly induced, required de novo protein synthesis, and was sustained at a high level for at least 23 h, Interestingly, PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells, In this paper, vue demonstrate that PIF is Egr-1 based on its recognition by anti-Egr-1 antisera in gel mobility shift assays, even though the IL-2R beta DNA binding motif differed substantially from the canonical Egr-1 binding site, In addition, Egr-1 bound to the Sp binding site. In Jurkat cells, both sites were required for maximal IL-2R beta promoter activity, and in HeLaS3 cells, transfection of Egr-1 could drive activity of a reporter construct containing both sites. Moreover, Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation, Thus, Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2R beta promoter activity.
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收藏
页码:3714 / 3722
页数:9
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