PROMOTER ANALYSIS OF THE GENE ENCODING THE I-KAPPA-B-ALPHA/MAD3 INHIBITOR OF NF-KAPPA-B - POSITIVE REGULATION BY MEMBERS OF THE REL/NF-KAPPA-B FAMILY
PROMOTER ANALYSIS OF THE GENE ENCODING THE I-KAPPA-B-ALPHA/MAD3 INHIBITOR OF NF-KAPPA-B - POSITIVE REGULATION BY MEMBERS OF THE REL/NF-KAPPA-B FAMILY
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DOI：
10.1002/j.1460-2075.1993.tb06197.x
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发表时间：
1993-12-15
期刊：
影响因子：
11.4
通讯作者：
ISRAEL, A
中科院分区：
文献类型：
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作者：
LEBAIL, O;SCHMIDTULLRICH, R;ISRAEL, A
为了表征编码转录因子NF-chiB的IchiB-α/MAD 3抑制剂的基因的调控，我们分离了人基因组克隆并对该基因的启动子进行了测序。MAD 3启动子在两个主要转录位点之一的上游显示出潜在的TATA元件，并含有几个潜在的NF-chiB结合序列，表明该基因受到该家族成员的正调控。转染实验表明，MAD 3启动子可以被rel/NF-chiB家族成员的各种组合以及佛波醇酯和肿瘤坏死因子激活。特异性缺失位于TATA盒上游37 bp的chiB基序之一，消除了对PMA和TNF的反应。该chiB基序结合NF-chiB（p50/relA）、p50/c-rel和relA/c-rel异源二聚体以及KBF 1（p50同源二聚体）。这些结果有助于解释先前观察到的NF-kappaB应答的瞬时性质：在NF-chiB活化后，抑制剂的表达增加，因此活性复合物的核转位程度降低，导致其靶基因的活化降低。
In order to characterize the regulation of the gene encoding the IchiB-alpha/MAD3 inhibitor of the transcription factor NF-chiB, we have isolated a human genomic clone and sequenced the promoter of this gene. The MAD3 promoter exhibits a potential TATA element upstream of one of the two major transcription sites, and contains several potential NF-chiB binding sequences, suggesting that the gene is positively regulated by members of this family. Transfection experiments demonstrate that the MAD3 promoter can be activated by various combinations of members of the rel/NF-chiB family, as well as by phorbol esters and tumor necrosis factor. Specific deletion of one of the chiB motifs, located 37 bp upstream of the TATA box, abolishes responses to PMA and TNF. This chiB motif binds NF-chiB (p50/relA), p50/c-rel and relA/c-rel heterodimers as well as KBF1 (p50 homodimer). These results help to explain the previously observed transient nature of the NF-kappaB response: following NF-chiB activation, the expression of the inhibitor is increased, therefore the extent of nuclear translocation of the active complex is reduced, resulting in a decreased activation of its target genes.