Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3 gene

被引:15
作者
Lin, Sen [2 ]
Li, Sufang [1 ]
Chen, Zan [1 ]
He, Xiangwei [1 ]
Zhang, Youyi [1 ]
Xu, Xiaojie [2 ]
Xu, Ming [1 ]
Yuan, Gu [2 ]
机构
[1] Peking Univ, Inst Vasc Med, Hosp 3, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing 100191, Peoples R China
[2] Peking Univ, Beijing Natl Lab Mol Sci BNLMS, Key Lab Bioorgan Chem & Mol Engn, Minist Educ,Dept Chem Biol,Coll Chem & Mol Engn, Beijing 100871, Peoples R China
基金
中国国家自然科学基金;
关键词
G-Quadruplex; 3'-Flanking region; Cepharanthine; STAT3; gene; Gene regulation; CIRCULAR-DICHROISM; MASS-SPECTROMETRY; TELOMERIC DNA; TUMOR-CELLS; BINDING; STABILIZATION; INHIBITION; MECHANISMS; CONVERSION; TETRAPLEX;
D O I
10.1016/j.bmcl.2011.07.121
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
G-Quadruplexes have been proved to exist in 5'-untranslated region (5'-UTR), promoter, intron and exon regions of many human genes. Here we report an intramolecular G-quadruplex formed by a G-rich sequence in the 3'-flanking region of signal transducers and activators of transcription 3 (STAT3) gene. The results showed that this G-rich sequence could affect the expression of STAT3. When the STAT3 G-quadruplex was stabilized by a novel non-planar ligand Cepharanthine (CEP), the decreased expression of STAT3 was observed in primary cultured cardiomyocytes. We also demonstrated that the down-regulation of STAT3 was most likely occurred at the transcriptional level. Our results provide a new clue for studying the G-quadruplex formation, recognition and function in the 3'-flanking region of gene. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5987 / 5991
页数:5
相关论文
共 37 条
[1]   Selective Targeting of G-Quadruplex Using Furan-Based Cyclic Homooligopeptides: Effect on c-MYC Expression [J].
Agarwal, Tani ;
Roy, Saumya ;
Chakraborty, Tushar Kanti ;
Maiti, Souvik .
BIOCHEMISTRY, 2010, 49 (38) :8388-8397
[2]   Solution structure of the biologically relevant g-quadruplex element in the human c-MYC promoter. implications for g-quadruplex stabilization [J].
Ambrus, A ;
Chen, D ;
Dai, JX ;
Jones, RA ;
Yang, DZ .
BIOCHEMISTRY, 2005, 44 (06) :2048-2058
[3]  
Balasubramanian S, 2006, RSC BIOMOL SCI, pV
[4]   A new steroid derivative stabilizes g-quadruplexes and induces telomere uncapping in human tumor cells [J].
Brassart, Bertrand ;
Gomez, Dennis ;
De Cian, Anne ;
Paterski, Rajaa ;
Montagnac, Alain ;
Qui, Khuong-Huu ;
Temime-Smaali, Nassima ;
Trentesaux, Chantal ;
Mergny, Jean-Louis ;
Gueritte, Franc Oise ;
Riou, Jean-Francois .
MOLECULAR PHARMACOLOGY, 2007, 72 (03) :631-640
[5]   Quadruplex DNA: sequence, topology and structure [J].
Burge, Sarah ;
Parkinson, Gary N. ;
Hazel, Pascale ;
Todd, Alan K. ;
Neidle, Stephen .
NUCLEIC ACIDS RESEARCH, 2006, 34 (19) :5402-5415
[6]   Tandem Application of Virtual Screening and NMR Experiments in the Discovery of Brand New DNA Quadruplex Groove Binders [J].
Cosconati, Sandro ;
Marinelli, Luciana ;
Trotta, Roberta ;
Virno, Ada ;
Mayol, Luciano ;
Novellino, Ettore ;
Olson, Arthur J. ;
Randazzo, Antonio .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (45) :16336-+
[7]   G-quartets 40 years later:: From 5′-GMP to molecular biology and supramolecular chemistry [J].
Davis, JT .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (06) :668-698
[8]   Reevaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action [J].
De Cian, Anne ;
Cristofari, Gael ;
Reichenbach, Patrick ;
De Lemos, Elsa ;
Monchaud, David ;
Teulade-Fichou, Marie-Paule ;
Shin-Ya, Kazuo ;
Lacroix, Laurent ;
Lingner, Joachim ;
Mergny, Jean-Louis .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (44) :17347-17352
[9]  
GUO KZ, 2007, ACTA PHARMACOL SIN, V28, P153
[10]   Many good reasons to have STAT3 in the heart [J].
Hilfiker-Kleiner, D ;
Hilfiker, A ;
Drexler, H .
PHARMACOLOGY & THERAPEUTICS, 2005, 107 (01) :131-137