Transcription of the RelB gene is regulated by NF-κB
Transcription of the RelB gene is regulated by NF-κB
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DOI：
10.1038/sj.onc.1204868
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发表时间：
2001-11-22
期刊：
影响因子：
8
通讯作者：
Paya, CV
中科院分区：
文献类型：
--
作者：
Bren, GD;Solan, NJ;Paya, CV
ReA和RelB是NF-kappaB家族的两个成员，在结构和功能上有所不同。虽然RelA通过抑制蛋白或I κ b的胞质定位而不是通过转录机制进行调控，但对RelB的调控知之甚少。在这项研究中，我们证明刺激（TNF或LPS）在几分钟内导致RelA的核易位，但需要数小时才能导致RelB的核易位。RelB的延迟核易位与其蛋白质合成的增加相关，这是继发于RelB基因转录的增加。仅RelA就足以诱导RelB基因转录并介导刺激驱动的RelB转录增加。RelB 5 '非翻译基因区域的克隆和表征表明，RelB转录依赖于含有两个NF-kappaB结合位点的TATA-less启动子。其中一个NF-kappaB位点主要参与p50的结合，而另一个位点则参与RelA和RelB的结合和转激活。最后，我们观察到p21，一种参与细胞周期控制和肿瘤发生的蛋白质，已知由NF-kappaB调节，在转录水平上被RelB上调。因此，至少在转录水平上，RelB以依赖RelA和RelB的方式受到调控，并可能在p21调控中发挥重要作用。
ReA and RelB are two members of the NF-kappaB family that differ structurally and functionally. While RelA is regulated through its cytosolic localization by inhibitor proteins or I kappaB and not through transcriptional mechanisms, the regulation of RelB is poorly understood. In this study we demonstrate that stimuli (TNF or LPS) lead within minutes to the nuclear translocation of RelA, but require hours to result in the nuclear translocation of RelB. The delayed nuclear translocation of RelB correlates with increases in its protein synthesis which are secondary to increases in RelB gene transcription. RelA is alone sufficient to induce RelB gene transcription and to mediate the stimuli-driven increase in RelB transcription. Cloning and characterization of the RelB 5 ' untranslated gene region indicates that RelB transcription is dependent on a TATA-less promoter containing two NF-kappaB binding sites. One of the NF-kappaB sites is primarily involved in the binding of p50 while the other one in the binding and transactivation by RelA and also RelB. Lastly, it is observed that p21, a protein involved in cell cycle control and oncogenesis known to be regulated by NF-kappaB, is upregulated at the transcriptional level by RelB. Thus, RelB is regulated at least at the level of transcription in a RelA and RelB dependent manner and may exert an important role in p21 regulation.