c-IAP2 is induced by ionizing radiation through NF-kappaB binding sites.

c-IAP2 is induced by ionizing radiation through NF-kappaB binding sites.
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c-IAP2 由电离辐射通过 NF-kappaB 结合位点诱导。

DOI:
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发表时间:
2001
期刊:
影响因子:
3.5
通讯作者:
S. Kizaka
S. Kizaka
中科院分区:
生物学3区
文献类型:
--
作者:
T. Ueda;N. Akiyama;H. Sai;N. Oya;M. Noda;M. Hiraoka;S. Kizaka

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对低剂量X射线辐射敏感的转录启动子可能有助于开发基因治疗与常规放射治疗相结合的新策略。逆转录病毒介导的基因陷阱筛选确定c-IAP 2为具有这种启动子的基因之一。对c-IAP 2启动子中X射线反应顺式元件的分析表明,NF-κ B结合位点是X射线反应所必需和充分的。我们构建了p4 NFB-BAX质粒,该质粒含有c-IAP 2启动子NF-κ B结合位点的四个串联重复序列(4 NFB)和一个受4 NFB控制的自杀基因BAX。用p4 NFB-BAX转染的人肿瘤细胞显著减少了在2戈伊照射下存活的细胞数量。
Transcriptional promoters responsive to low doses of X-irradiation may be useful in developing a new strategy in gene therapy combined with conventional radiotherapy. The retrovirus-mediated gene trap screening identified c-IAP2 as one of genes possessing such promoters. The analysis of the cis-elements responsive to X-irradiation in c-IAP2 promoter revealed that the NF-kappaB binding sites were necessary and sufficient for the X-ray-responsiveness. We constructed the plasmid p4NFB-BAX, which had four tandem repeats of the NF-kappaB binding sites of c-IAP2 promoter (4NFB) and a suicide gene BAX under the control of 4NFB. The human tumor cells transfected with p4NFB-BAX significantly reduced the number of cells that survived 2 Gy irradiation.