FOS AND JUN REPRESS TRANSCRIPTION ACTIVATION BY NF-IL6 THROUGH ASSOCIATION AT THE BASIC ZIPPER REGION
FOS AND JUN REPRESS TRANSCRIPTION ACTIVATION BY NF-IL6 THROUGH ASSOCIATION AT THE BASIC ZIPPER REGION
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DOI：
10.1128/mcb.14.1.268
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发表时间：
1994-01-01
影响因子：
5.3
通讯作者：
CHENKIANG, S
中科院分区：
文献类型：
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作者：
HSU, W;KERPPOLA, TK;CHENKIANG, S
NF-IL-6和AP-1家族转录因子在细胞类型特异性方式下被白细胞介素-6（IL-6）协同诱导，表明它们在细胞核中介导IL-6信号。我们表明，碱性亮氨酸拉链（bZIP）区域的NF-白细胞介素6介导的直接关联与bZIP区域的Fos和Jun在体外。这种相互作用不依赖于它们的同源识别DNA元件的存在或任一配偶体的翻译后修饰。NF-IL 6同源二聚体可以结合NF-IL 6和AP-1位点，而Fos和Jun不能结合大多数NF-IL 6位点。与Fos或与Jun的跨家族关联改变了NF-IL 6的DNA结合特异性并降低了其与NF-IL 6位点的结合。翻译起始位点不同的NF-IL 6同种型具有不同的转录活性。在瞬时转染试验中，Fos和Jun抑制了与NF-IL 6位点连接的报告基因被NF-IL 6激活。因此，与AP-1的结合导致NF-1 L 6对转录激活的抑制。抑制是NF-IL 6位点依赖性的，并且可能在确定IL-6信号传导中的启动子和细胞类型特异性中起作用。
NF-IL6 and AP-1 family transcription factors are coordinately induced by interleukin-6 (IL-6) in a cell-type-specific manner, suggesting that they mediate IL-6 signals in the nucleus. We show that the basic leucine zipper (bZIP) region of NF-IL6 mediates a direct association with the bZIP regions of Fos and Jun in vitro. This interaction does not depend on the presence of their cognate recognition DNA elements or the posttranslational modification of either partner. NF-IL6 homodimers can bind to both NF-IL6 and AP-1 sites, whereas Fos and Jun cannot bind to most NF-IL6 sites. Cross-family association with Fos or with Jun alters the DNA binding specificity of NF-IL6 and reduced its binding to NF-IL6 sites. NF-IL6 isoforms that differ in the site of translation initiation have distinct transcriptional activities. Activation of a reporter gene linked to the NF-IL6 site by NF-IL6 is repressed by Fos and by Jun in transient transfection assays. Thus, association with AP-1 results in repression of transcription activation by NF-IL6. The repression is NF-IL6 site dependent and may have a role in determining the promoter and cell type specificity in IL-6 signaling.