Induction of the TRAIL receptor KILLER/DR5 in p53-dependent apoptosis but not growth arrest
Induction of the TRAIL receptor KILLER/DR5 in p53-dependent apoptosis but not growth arrest
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DOI：
10.1038/sj.onc.1203025
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发表时间：
1999-11
期刊：
影响因子：
8
通讯作者：
Gen Sheng Wu;Timothy F Burns;E Robert McDonald III;Ray Meng;G. Kao;R. Muschel;T. Yen;W. El-Deiry
中科院分区：
文献类型：
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作者：
Gen Sheng Wu;Timothy F Burns;E Robert McDonald III;Ray Meng;G. Kao;R. Muschel;T. Yen;W. El-Deiry
TRAIL死亡受体KILLER/DR 5在野生型p53表达细胞中由DNA损伤剂诱导。在这里，我们表明，与p53靶向CDK抑制剂p21 WAF 1/CIP 1不同，TRAIL死亡受体KILLER/DR 5仅在经历p53依赖性凋亡的细胞中诱导，而不是细胞周期停滞。因此，携带诱导型MMT驱动的p53基因的GM胶质母细胞瘤细胞经历细胞周期停滞，并且在地塞米松暴露后上调p21而不是KILLER/DR 5表达。WI 38正常肺成纤维细胞在电离辐射后经历细胞周期阻滞，也诱导p21基因表达，但不诱导KILLER/DR 5基因表达。KILLER/DR 5上调在来自共济失调毛细血管扩张症患者的辐射淋巴母细胞中也是缺乏的，这表明ATM-p53途径在DNA损伤后调节KILLER/DR 5表达中的作用。在经历p53依赖性凋亡的细胞中，放线菌素D抑制转录阻断KILLER/DR 5和p21诱导。我们的研究结果表明，KILLER/DR 5死亡受体的p53依赖性转录诱导仅限于细胞发生凋亡，而不是细胞发生完全p53依赖性G1期阻滞。
The TRAIL death receptor KILLER/DR5 is induced by DNA damaging agents in wild-type p53-expressing cells. Here we show that, unlike the p53-target CDK-inhibitor p21 WAF1/CIP1, the TRAIL death receptor KILLER/DR5 is only induced in cells undergoing p53-dependent apoptosis and not cell cycle arrest. Thus GM glioblastoma cells carrying an inducible MMTV-driven p53 gene undergo cell cycle arrest and upregulate p21 but not KILLER/DR5 expression upon dexamethasone exposure. WI38 normal lung fibroblasts undergoing cell cycle arrest in response to ionizing irradiation also induce p21 but not KILLER/DR5 gene expression. KILLER/DR5 upregulation is also deficient in irradiated lymphoblastoid cells derived from patients with Ataxia Teleangiectasia suggesting a role for the ATM-p53 pathway in regulating KILLER/DR5 expression after DNA damage. Inhibition of transcription by Actinomycin D blocks both KILLER/DR5 and p21 induction in cells undergoing p53-dependent apoptosis. Our results suggest that the p53-dependent transcriptional induction of KILLER/DR5 death receptor is restricted to cells undergoing apoptosis and not cells undergoing exclusively p53-dependent G1 arrest.