Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner

Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner
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DOI:
10.1016/j.bbrc.2006.01.119
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发表时间:
2006-03-31
影响因子:
3.1
通讯作者:
Kobayashi, M
Kobayashi, M
中科院分区:
生物学4区
文献类型:
--
作者:
Aoki, S;Kong, DX;Kobayashi, M

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Aaptamine(一种苯并萘啶生物碱)是在使用转染的人骨肉瘤 MG63 细胞 (MG63luc(+)) 进行生物测定的指导下从海绵中分离出来的。 Aaptamine在20-50μM的浓度下剂量依赖性地激活稳定转染的MG63细胞中的p21启动子。通过aaptamine处理也增加了野生型MG63细胞中p21及其mRNA的表达。此外,通过aaptamine处理,MG63细胞的细胞周期在48小时内被阻滞在G2/M期。为了分析p21启动子在aaptamine上调p21中的响应元件,用一系列缺失或突变的启动子片段瞬时转染MG63细胞;并通过使用这些相应的转染细胞检查用适体胺处理诱导荧光素酶。适体胺对 p21 启动子的激活是通过 -82 和 -50 之间的 Sp1 位点以不依赖于 p53 的方式进行的。 (c) 2006 Elsevier Inc. 保留所有权利。
Aaptamine, a benzonaphthyridine alkaloid was isolated from a marine sponge on the guidance of a bioassay using the transfected human osteosarconra MG63 cells (MG63luc(+)). Aaptamine activated p21 promoter stably transfected in MG63 cells dose-dependently at the concentrations of 20-50 mu M. Expression of p21 and its mRNA in the wild-type MG63 cells also increased by aaptamine-treatment. Furthermore, the cell cycle of MG63 cells was arrested at the G2/M phase within 48 h by the aaptamine-treatment. To analyze a responive element of p21 promoter in the up-regulation of p21 by aaptamine, MG63 cells were transiently transfected with a series of the deleted or mutated promoter segments; and induction of luciferase with aaptamine treatment was examined by using these corresponding transfected cells. The activation of p21 promoter by aaptamine was led through acting Sp1 sites between -82 and -50 by in a p53-independent manner. (c) 2006 Elsevier Inc. All rights reserved.