Cyclosporin A-sensitive transcription factor Egr-3 regulates Fas ligand expression

被引:144
作者
Mittelstadt, PR [1 ]
Ashwell, JD [1 ]
机构
[1] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1128/MCB.18.7.3744
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
Activation-induced transcriptional upregulation of the ligand for Fas (FasL) and the resulting apoptosis of Fas-bearing cells constitute essential steps in a host of normal and pathological processes. Here we describe an activation-inducible cis acting regulatory element in the fasL promoter that is required for gene expression. Oligonucleotide competition and antibody supershift analyses identified two activation-induced DNA binding species: Egr-1 (NGFI-A, krox-24, zif268, TIS-I), a transcription factor that has been implicated in growth, differentiation, and apoptosis; and Egr-3 (PILOT), a transcription factor of no previously known function, Activation-induced expression of Egr-3, like that of FasL, was inhibited by cyclosporin A, whereas expression of Egr-1 was unaffected, Transient expression of Egr-3 alone increased fasL promoter activity in a cyclosporin A-insensitive manner, whereas expression of Egr-1 had little effect. Moreover, endogenous fast mRNA was induced in nonlymphoid cells by forced expression of Egr-3 in the absence of any other stimulus. These studies identify a critical Egr family-binding site in the fasL promoter and demonstrate that activation-induced Egr-3, but not Egr-1, directly upregulates fast transcription in response to activating stimuli.
引用
收藏
页码:3744 / 3751
页数:8
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