CORRECTION OF RADIATION SENSITIVITY IN ATAXIA-TELANGIECTASIA CELLS BY A TRUNCATED I-KAPPA-B-ALPHA
CORRECTION OF RADIATION SENSITIVITY IN ATAXIA-TELANGIECTASIA CELLS BY A TRUNCATED I-KAPPA-B-ALPHA
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DOI：
10.1126/science.7777860
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发表时间：
1995-06-16
期刊：
影响因子：
56.9
通讯作者：
DRITSCHILO, A
中科院分区：
文献类型：
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作者：
JUNG, M;ZHANG, Y;DRITSCHILO, A
共济失调性毛细血管扩张 (AT) 患者的细胞对电离辐射过敏，并且在 DNA 合成调节方面存在缺陷。通过表达克隆分离出一种互补 DNA，可纠正 AT D 组患者成纤维细胞中的辐射敏感性和 DNA 合成缺陷，并显示其编码截短形式的 I kappa B-alpha，一种核因子 kappa B (NF-kappa B) 转录激活剂的抑制剂。亲本 AT 成纤维细胞表达大量 I kappa B-α 转录物，并显示 NF-kappa B 的组成型激活。用截短的 I kappa B-α 转染的 AT 成纤维细胞表达正常量的 I kappa B-α 转录物，并显示 NF-kappa B 的调节激活。这些结果表明 NF-kappa B 和 I kappa B-α 的异常调节导致细胞缺陷在。
Cells from patients with ataxia telangiectasia (AT) are hypersensitive to ionizing radiation and are defective in the regulation of DNA synthesis. A complementary DNA that corrects the radiation sensitivity and DNA synthesis defects in fibroblasts from an AT group D patient was isolated by expression cloning and shown to encode a truncated form of I kappa B-alpha, an inhibitor of the nuclear factor kappa B (NF-kappa B) transcriptional activator. The parental AT fibroblasts expressed large amounts of the I kappa B-alpha transcript and showed constitutive activation of NF-kappa B. The AT fibroblasts transfected with the truncated I kappa B-alpha expressed normal amounts of the I kappa B-alpha transcript and showed regulated activation of NF-kappa B. These results suggest that aberrant regulation of NF-kappa B and I kappa B-alpha contribute to the cellular defect in AT.