Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter.

Journal of the American Chemical Society
Thomas S DexheimerLaurence H Hurley

Abstract

The human bcl-2 gene contains a GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of bcl-2 gene expression. We have demonstrated that the guanine-rich strand of the DNA in this region can form any one of three distinct intramolecular G-quadruplex structures. Mutation and deletion analysis permitted isolation and identification of three overlapping DNA sequences within this element that formed the three individual G-quadruplexes. Each of these was characterized using nondenaturing gel analysis, DMS footprinting, and circular dichroism. The central G-quadruplex, which is the most stable, forms a mixed parallel/antiparallel structure consisting of three tetrads connected by loops of one, seven, and three bases. Three different G-quadruplex-interactive agents were found to further stabilize these structures, with individual selectivity toward one or more of these G-quadruplexes. Collectively, these results suggest that the multiple G-quadruplexes identified in the promoter region of the bcl-2 gene are likely to play a similar role to the G-quadruplexes in the c-myc promoter in that their formation could serve to modulate gene transcription. Last, we demonstrate that the compl...Continue Reading

References

Apr 18, 1991·Nature·E H Blackburn
Jan 25, 1992·Nucleic Acids Research·M C Hammond-KosackM W Kilpatrick
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·Y Tsujimoto, C M Croce
Jul 15, 1983·Science·J J Yunis
Sep 1, 1995·Stroke; a Journal of Cerebral Circulation·M D LinnikH J Federoff
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·P G FarlieO Bernard
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Dubois-DauphinJ C Martinou
Jan 1, 1994·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J C ReedT Miyashita
Sep 2, 1993·The New England Journal of Medicine·F PezzellaD Y Mason
Aug 1, 1997·The Journal of Biological Chemistry·C HeckmanL M Boxer
Feb 18, 1998·American Journal of Obstetrics and Gynecology·W TjalmaP van Dam
Apr 4, 1998·Nucleic Acids Research·T SimonssonM Kubista
May 23, 1998·Annual Review of Immunology·D T Chao, S J Korsmeyer
Sep 12, 1998·Science·J M Adams, S Cory
Dec 24, 1998·Nucleic Acids Research·H HanM Salazar
Apr 27, 1999·Journal of Biomolecular Structure & Dynamics·X G SunJ F Qin
Feb 29, 2000·The Journal of Biological Chemistry·C A HeckmanL M Boxer
Mar 31, 2000·Pharmacology & Therapeutics·L H HurleyD D Von Hoff
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·A LewG C Kennedy
Feb 15, 2001·Nature Cell Biology·S P TzungD M Hockenbery
Jul 18, 2001·Journal of the American Chemical Society·K Shin-yaH Seto
Sep 13, 2001·Journal of the American Chemical Society·H HanL H Hurley
Dec 1, 2001·Journal of Medicinal Chemistry·I J EnyedyS Wang
May 29, 2002·Oncogene·Caroline A HeckmanLinda M Boxer
Aug 7, 2002·Antisense & Nucleic Acid Drug Development·Richard J KlasaStanley R Frankel
Aug 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Adam Siddiqui-JainLaurence H Hurley
Oct 9, 2002·Mini Reviews in Medicinal Chemistry·P J Perry, T C Jenkins
Feb 13, 2003·Nucleic Acids Research·Daisuke MiyoshiNaoki Sugimoto
Apr 12, 2003·Nucleic Acids Research·Virna DapićPaula J Bates
Apr 17, 2003·Journal of the American Chemical Society·Marie-Paule Teulade-FichouW David Wilson
Sep 13, 2003·Oncogene·Caroline A HeckmanLinda M Boxer
Jan 1, 1953·Cold Spring Harbor Symposia on Quantitative Biology·J D WATSON, F H CRICK
Oct 3, 2003·Journal of Medicinal Chemistry·R John HarrisonStephen Neidle
Jul 15, 2004·Journal of the American Chemical Society·Jeyaprakashnarayanan SeenisamyLaurence H Hurley
Jul 15, 2004·Journal of the American Chemical Society·Anh Tuân PhanDinshaw J Patel

❮ Previous
Next ❯

Citations

Jun 29, 2007·European Biophysics Journal : EBJ·Max A Keniry, Elisabeth A Owen
Dec 15, 2012·Journal of Computer-aided Molecular Design·Jin-Qiang HouZhi-Shu Huang
Aug 4, 2007·Journal of the American Chemical Society·Kexiao GuoLaurence H Hurley
Aug 20, 2009·Journal of the American Chemical Society·Zoë A E WallerShankar Balasubramanian
Nov 17, 2009·Journal of the American Chemical Society·Samantha KendrickLaurence H Hurley
Nov 13, 2009·Nature Reviews. Cancer·Tracy A Brooks, Laurence H Hurley
Apr 2, 2011·Nature Reviews. Drug Discovery·Shankar BalasubramanianStephen Neidle
Mar 14, 2008·Chemical Communications : Chem Comm·Zoë A E WallerShankar Balasubramanian
Feb 26, 2009·Chemical Communications : Chem Comm·Anton GranzhanKatharina Jäger
Mar 25, 2011·Chemical Communications : Chem Comm·Yu-Jing LuKwok-Yin Wong
Dec 19, 2012·Journal of Biomolecular Structure & Dynamics·Rajiv Kumar KarSubhrangsu Chatterjee
Apr 22, 2010·Nucleosides, Nucleotides & Nucleic Acids·Mingyue TianYalin Tang
Oct 3, 2006·Nucleic Acids Research·Sarah BurgeStephen Neidle
Dec 26, 2007·Nucleic Acids Research·Jun TangZheng Tan
Jun 20, 2007·Nucleic Acids Research·Phillip A RachwalKeith R Fox
Mar 6, 2009·Nucleic Acids Research·Jin-li ZhangFeng Geng
Sep 18, 2009·Nucleic Acids Research·Zhuo DuNing Li
Sep 12, 2009·Nucleic Acids Research·Himesh FernandoShankar Balasubramanian
Oct 13, 2009·Nucleic Acids Research·Mykola I OnyshchenkoIgor G Panyutin
May 5, 2011·Nucleic Acids Research·Xiaotian TongChunyang Cao
May 20, 2011·Nucleic Acids Research·Mykola I OnyshchenkoIgor G Panyutin
Jul 1, 2011·Nucleic Acids Research·Yu-Lin TsaiTa-Chau Chang
Sep 7, 2011·Nucleic Acids Research·Roman V ReshetnikovAndrey V Golovin
Oct 9, 2009·BMC Structural Biology·Federico FogolariLuigi E Xodo
Jun 12, 2013·PloS One·Wataru YoshidaKazunori Ikebukuro
Aug 21, 2010·Journal of Nucleic Acids·David MonchaudMarie-Paule Teulade-Fichou
Jun 22, 2010·Future Medicinal Chemistry·Danzhou Yang, Keika Okamoto

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.