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学科主题: 临床医学
题名:
Exploring the Formation and Recognition of an Important G-Quadruplex in a HIF1 alpha Promoter and Its Transcriptional Inhibition by a Benzo[c]phenanthridine Derivative
作者: Chen, Han1; Long, Haitao1,3; Cui, Xiaojie1; Zhou, Jiang1; Xu, Ming2; Yuan, Gu1
刊名: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
发表日期: 2014-02-12
DOI: 10.1021/ja412128w
卷: 136, 期:6, 页:2583-2591
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary
研究领域[WOS]: Chemistry
关键词[WOS]: INDUCIBLE FACTOR-I ; CIRCULAR-DICHROISM ; CANCER-THERAPY ; MESSENGER-RNA ; HYPOXIA ; HIF-1 ; GENE ; SITE ; ANGIOGENESIS ; SELECTIVITY
英文摘要:

Four putative G-quadruplex sequences (PGSs) in the HIF1 alpha promoter and the 5′UTR were evaluated for their G-quadruplex-forming potential using ESI-MS, CD, FRET, DMS footprinting, and a polymerase stop assay. An important G-quadruplex (S1) has been proven to inhibit HIF1 alpha transcription by. blocking AP2 binding. A benzo[c]phenanthridine derivative was found to target the S1 G-quadruplex and induce its conformational conversion from antiparallel to parallel orientation. The transcriptional suppression of HIF1 alpha by this compound was demonstrated using western blotting, Q-RT-PCR, luciferase assay, and ChIP. Our new findings provided a novel strategy for HIF1 alpha regulation and potential insight for cancer therapy.

语种: 英语
所属项目编号: 2012CB720600 ; 2012CB720601 ; 21372021
项目资助者: 973 Program ; National Natural Science Foundation of China
WOS记录号: WOS:000331343300058
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64046
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Peking Univ, Dept Biol Chem, Beijing Natl Lab Mol Sci,Coll Chem & Mol Engn, Key Lab Bioorgan Chem & Mol Engn,Minist Educ, Beijing 100871, Peoples R China
2.Peking Univ, Hosp 3, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
3.Beijing Inst Technol, Sch Chem, Beijing 100081, Peoples R China

Recommended Citation:
Chen, Han,Long, Haitao,Cui, Xiaojie,et al. Exploring the Formation and Recognition of an Important G-Quadruplex in a HIF1 alpha Promoter and Its Transcriptional Inhibition by a Benzo[c]phenanthridine Derivative[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2014,136(6):2583-2591.
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