Involvement of two NF-κB binding elements in tumor necrosis factor α, CD40, and Epstein-Barr virus latent membrane protein 1-mediated induction of the cellular inhibitor of apoptosis protein 2 gene
Involvement of two NF-κB binding elements in tumor necrosis factor α, CD40, and Epstein-Barr virus latent membrane protein 1-mediated induction of the cellular inhibitor of apoptosis protein 2 gene
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DOI：
10.1074/jbc.m001202200
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发表时间：
2000-06-16
影响因子：
4.8
通讯作者：
Lee, TH
中科院分区：
文献类型：
--
作者：
Hong, SY;Yoon, WH;Lee, TH
NF-κ B的抗凋亡功能被认为是通过诱导抗凋亡基因介导的。在抗凋亡基因中，细胞凋亡抑制蛋白2（c-IAP 2/HIAP-1/MHC）最初被鉴定为募集到肿瘤坏死因子（TNF）受体复合物的分子，并且其表达优先被TNF和其他激活NF-κ B的刺激物上调。然而，NF-κ B B对c-IAP 2基因转录调控的直接证据仍然缺失。在这里，我们已经克隆和表征的启动子区所需的NF-κ B依赖转录的c-IAP 2基因。对c-IAP 2基因5 '侧翼区的3.5-腺苷酸酶片段进行测序，鉴定了TATA样序列和活化T细胞核因子、干扰素调节因子1、激活蛋白1、糖皮质激素反应元件和三种推定的NF-κ B结合元件的潜在结合位点。与荧光素酶基因连接的5 '侧翼区的缺失和突变分析揭示，TNF或白细胞介素1的转录激活由两个NF-κ B结合位点协同介导。电泳迁移率变动分析的特征在于两个NF-κ B位点可以被NF-κ B p50/p65异二聚体识别和结合。另外，当CD 40或EB病毒潜伏膜蛋白1过表达时，c-IAP 2启动子的转录被强烈上调。
The antiapoptotic function of NF-kappa B is believed to be mediated through the induction of antiapoptotic genes. Among the antiapoptotic genes, cellular inhibitor of apoptosis protein 2 (c-IAP2/HIAP-1/MHC) is originally identified as a molecule recruited to the tumor necrosis factor (TNF) receptor complex, and its expression is preferentially up-regulated by TNF and other stimuli activating NF-kappa B. However, direct evidence of transcriptional regulation of NF-kappa B on the c-IAP2 gene is still missing. Here, we have cloned and characterized the promoter region required for NF-kappa B-dependent transcription of the c-IAP2 gene. Sequencing of a 3.5-kilobase fragment of the 5'-flanking region of the c-IAP2 gene has identified a TATA-like sequence and potential binding sites for nuclear factor of activated T cells, interferon regulatory factor 1, activator protein 1, glucocorticoid response element, and three putative NF-kappa B binding elements. Deletion and mutational analysis of the 5'-flanking region linked to the luciferase gene revealed that transcriptional activation by TNF or interleukin 1 is mediated cooperatively by two NF-kappa B binding sites. Electrophoretic mobility shift assays characterized that the two NF-kappa B sites can be recognized and bound by the NF-kappa B p50/p65 heterodimer. In addition, the transcription of c-IAP2 promoter was strongly up-regulated when CD40 or Epstein-Barr virus latent membrane protein 1 was overexpressed.