c-Myc部分通过调控Nbs1减弱阿霉素降低U2OS细胞集落形成的能力(英文)  

c-Myc Attenuates The Ability of Doxorubicin to Reduce The Colony Formation Partially Through Regulating Nbs1 in U2OS Cells

作　　者：施寒清[1,2] 黄慧[1] 张玺涛[1] 张建超[1] 雒秀坦[1] 彭秀娥[1] 黄百渠[1] 陆军[1] 

机构地区：[1]东北师范大学遗传与细胞研究所教育部表观遗传重点实验室,长春130024 [2]大庆石油学院石油工程学院,大庆163318

出　　处：《生物化学与生物物理进展》2010年第8期855-863,共9页Progress In Biochemistry and Biophysics

基　　金：supported by grants from National Basic Research Program of China(2005CB522404,2006CB910506);The Program for Changjiang Scholars and Innovative Research Team(PCSIRT)in Universities(IRT0519);The National Natural Science Foundation of China(30771232,30671184)~~

摘　　要：c-Myc是一种泛在性的转录因子,它调控着许多涉及细胞增殖、分化、凋亡等生命活动的基因.实验结果表明在骨肉瘤细胞U2OS中过表达c-Myc和Nbs1都能减弱阿霉素降低集落形成的能力.进一步的实验证实c-Myc的这种作用与Nbs1有关,Nbs1是c-Myc的靶基因.染色质免疫沉淀实验显示,c-Myc招募组蛋白乙酰化酶p300复合物到Nbs1启动子区,引起了组蛋白H4的乙酰化,定位在Nbs1启动子区的相邻的两个E-box对c-Myc的结合是必要的.上述结果说明c-Myc减弱阿霉素的作用部分是通过调控Nbs1来实现的.这也提示了c-Myc在阿霉素诱导的DNA损伤修复中起作用。c-Myc is a ubiquitous transcription factor that regulates a wide variety of genes involved in the control of cell proliferation,differentiation and apoptosis.It was demonstrated that over-expressions of c-Myc and Nbs1 attenuated the ability of doxorubicin in reduction of colony formation in U2OS cells,and it was found that this effect of c-Myc was associated with Nbs1.It can be confirmed that Nbs1 is a target gene of c-Myc.Chromatin immunoprecipitation assays reveal that c-Myc recruited the histone acetyltransferase p300 complex to the promoter region of Nbs1 gene,resulting in an increased level of acetylated histone H4.Furthermore,it was found that the two proximal E-box elements located in Nbs1 promoter region were essential for the c-Myc binding.Thus,it was concluded that c-Myc attenuates the effect of doxorubicin partially through regulating Nbs1,implicating its roles in repair of DNA breakage induced by doxorubicin.

关 键 词：C-MYC Nbs1 阿霉素 集落形成 P300 

分 类 号：Q5[生物学—生物化学] Q7