CCND1启动子区串联四链体的形成、识别与转录抑制
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- 英文论文题名：Formation,recognition and transcriptional inhibition of tandem G-quadruplex structures from CCND1 proximal promoter
- 论文作者：谭伟 ; 张录录 ; 周江 ; 徐明 ; 袁谷
- 英文论文作者：Wei Tan ; Lulu Zhang ; Jiang Zhou ; Ming Xu ; Gu Yuan ; College of chemistry and molecular engineering ; Peking University ; Department of Cardiology ; Peking University Third Hospital
- 年：2016
- 作者机构：北京大学化学与分子工程学院;北京大学第三医院心血管内科;
- 论文关键词：串联四链体 ; CCND1 ; 防己诺林碱
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：R730.2
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：170k
- 原文格式：D
- 会议级别：全国
摘要
癌基因CCND1的异常过度表达与多种人类癌症相关,因此下调其表达将是治疗癌症的一种有前途的方法。在CCND1近侧启动子区有一条复杂的富嘌呤序列,其含有八处连续嘌呤带,并有三处Sp1转录因子的结合位点。本研究显示该序列可以自我折叠形成一个由12碱基连接起的串联平行四链体结构,并能够负调控CCND1启动子区的转录。同时,发现一个天然生物碱防己诺林碱与这个串联四链体具有良好的结合性,且具有相对双链DNA的四链体高选择性。研究表明防己诺林碱能通过取代Sp1转录因子与四链体的结合,有效抑制CCND1的活性,从而指出了直接下调CCND1基因用于癌症治疗的一个新靶点和新途径。
CCND1 is solidly established as an oncogene and its aberrant over-expression drives many types of human cancers.Here,we revealed that a guanine-rich sequence from CCND1 promoter can folded into tandem parallel folded G-quadruplex motifs connected by a 12-nt linker,which were identified to be negative transcriptional regulator in the CCND1 promoter.Moreover,we found that fangchinoline,a natural alkaloid,had a high binding affinity with the CCND1 tandem G-quadruplexes and had a remarkable G-quadruplex/duplex selectivity.The targeting of the tandem G-quadruplexes by fangchinoline effectively inhibited CCND1 activities,therefore this research reveals a possible strategy to directly down-regulate CCND1 for cancer therapy.
CCND1 is solidly established as an oncogene and its aberrant over-expression drives many types of human cancers.Here,we revealed that a guanine-rich sequence from CCND1 promoter can folded into tandem parallel folded G-quadruplex motifs connected by a 12-nt linker,which were identified to be negative transcriptional regulator in the CCND1 promoter.Moreover,we found that fangchinoline,a natural alkaloid,had a high binding affinity with the CCND1 tandem G-quadruplexes and had a remarkable G-quadruplex/duplex selectivity.The targeting of the tandem G-quadruplexes by fangchinoline effectively inhibited CCND1 activities,therefore this research reveals a possible strategy to directly down-regulate CCND1 for cancer therapy.
引文
[1]Mukundan,V.T.;Do,N.Q.;Phan,A.T.Nucleic Acids Res.2011,39:8984.
[2]Yuan,G.;Zhang,Q.;Zhou,J.;Li,H.H.Mass Spectrom.Rev.2011,30:1121.
[2]Yuan,G.;Zhang,Q.;Zhou,J.;Li,H.H.Mass Spectrom.Rev.2011,30:1121.