DNA topoisomerase II poison TAS-103 transactivates GC-Box-dependent transcription via acetylation of Sp1
DNA topoisomerase II poison TAS-103 transactivates GC-Box-dependent transcription via acetylation of Sp1
复制标题
DOI：
10.1074/jbc.m410499200
复制
发表时间：
2005-01-14
影响因子：
4.8
通讯作者：
Kohno, K
中科院分区：
文献类型：
--
作者：
Torigoe, T;Izumi, H;Kohno, K
药物诱导的转录因子修饰在细胞凋亡和生存信号传导中都起着重要作用。本文的数据表明，DNA拓扑异构酶II毒性TAS-103以gc -box依赖的方式反激活了SV40启动子，并在表达p300的细胞中诱导Sp1乙酰化。在缺乏p300的细胞中没有观察到这种活性。TAS-103处理也增加了细胞核中p300的含量以及p300与Sp1的相互作用。细胞对TAS-103的易感性与p300的表达相关，而与拓扑异构酶II的表达无关。此外，p300的存在使癌细胞对TAS-103显着增敏，而对顺铂没有增敏作用。综上所述，这些发现证明了抗癌药物对凋亡通路中Sp1乙酰化和Sp1依赖转录的新基因组反应。
Drug-induced modifications of transcription factors play important roles in both apoptosis and survival signaling. The data presented here show that the DNA topoisomerase II poison TAS-103 transactivated the SV40 promoter in a GC-box-dependent manner and induced Sp1 acetylation in cells expressing p300. This activity was not observed in cells lacking p300. TAS-103 treatment also enhanced the p300 content of the nucleus and the interaction of p300 with Sp1. Cellular susceptibility to TAS-103 was correlated with p300 expression but not with topoisomerase II expression. Furthermore, the presence of p300 significantly sensitized cancer cells to TAS-103 but not to cisplatin. Taken together, these findings demonstrate novel genomic responses to anticancer agents that modulate Sp1 acetylation and Sp1-dependent transcription in an apoptotic pathway.