title: A newly identified G-quadruplex as a potential target regulating Bcl-2 expression.
abstract: BACKGROUND
  A new G-quadruplex structure located in the B-cell CLL/lymphoma 2 (Bcl-2) P1 promoter and its physiological function related to Bcl-2 transcription have been studied to find a potential anticancer therapeutic target.
  
  
  METHODS
  Absorption, polyacrylamide gel electrophoresis, fluorescence, circular dichroism, and nuclear magnetic resonance spectra have been employed to determine G-quadruplex structure and the interaction between G-quadruplex and phenanthrolin-dicarboxylate. Real time polymerase chain reaction and luciferase assay were done to assess the physiological function of the G-quadruplex structure.
  
  
  RESULTS
  The UV-melting and polyacrylamide gel electrophoresis studies show that the p32 DNA sequence forms an intramolecular G-quadruplex structure. Circular dichroism and nuclear magnetic resonance spectra indicate that the G-quadruplex is a hybrid-type structure with four G-tetrads. Fluorescence spectra show that a phenanthroline derivative has a higher binding affinity for p32 G-quadruplex than duplex. Further circular dichroism and nuclear magnetic resonance studies indicate that the phenanthroline derivative can regulate p32 G-quadruplex conformation. Real time polymerase chain reaction and luciferase assays show that the phenanthroline derivative has down-modulated Bcl-2 transcription activity in a concentration-dependent manner. However, no such effect was observed when p32 G-quadruplex was denatured through base mutation.
  
  
  CONCLUSIONS
  The newly identified G-quadruplex located in the P1 promoter of Bcl-2 oncogene is intimately related with Bcl-2 transcription activity, which may be a promising anticancer therapeutic target.
  
  
  CONCLUSIONS
  The newly identified G-quadruplex in the Bcl-2 P1 promoter may be a novel anticancer therapeutic target.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: hongxsun@iccas.ac.cn.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Sun
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Yuquan Road 19(A), Shijingshan District, Beijing 100049, PR China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Qianfan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Aijiao
authors.initials: A
authors.lastname: Guan
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Yuquan Road 19(A), Shijingshan District, Beijing 100049, PR China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Yu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: tangyl@iccas.ac.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D054856:G-Quadruplexes; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Anticancer therapeutic target; Bcl-2 P1 promoter; Dual-luciferase reporter assay; G-quadruplex; Phenanthrolin-dicarboxylate; Spectroscopy