Novel molecular mechanism for actinomycin D activity as an oncogenic promoter G-quadruplex binder. Kang, H. & Park, H. Biochemistry, 48(31):7392–8, August, 2009. ![Novel molecular mechanism for actinomycin D activity as an oncogenic promoter G-quadruplex binder. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Actinomycin D (ActD) is a natural antibiotic that inhibits the transcription of genes by interacting with a GC-rich duplex, a single-stranded or hairpin form of DNA, and then interfering with the action of RNA polymerase. In this study, we identified a novel molecular mechanism of anticancer activity of ActD as an oncogenic c-Myc promoter G-quadruplex binder. ActD selectively inhibits the elongation of oligonucleotides containing c-Myc promoter G-quadruplex sequence in PCR-stop assays. UV-vis spectroscopic and circular dichroism studies suggest that ActD interacts with c-Myc promoter G-quadruplex via a surface end stacking interaction, inducing a mixed-type conformation of the G-quadruplex. ActD selectively inhibits the cellular growth and synthesis of c-Myc mRNA in Ramos cells having the NHEIII(1) region in the translocated c-Myc gene. In addition, the results of promoter assays using two kinds of NHEIII(1) region mutants and wild-type constructs strongly support the idea that binding of ActD with G-quadruplex formed in the promoter region results in the reporter gene being turned off. Our study reveals a novel mechanism underlying the anticancer activity of ActD, whereby ActD interacts with oncogenic promoter G-quadruplex DNA to repress gene expression.
@article{Kang2009,
title = {Novel molecular mechanism for actinomycin {D} activity as an oncogenic promoter {G}-quadruplex binder.},
volume = {48},
issn = {1520-4995},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19496619},
doi = {10.1021/bi9006836},
abstract = {Actinomycin D (ActD) is a natural antibiotic that inhibits the transcription of genes by interacting with a GC-rich duplex, a single-stranded or hairpin form of DNA, and then interfering with the action of RNA polymerase. In this study, we identified a novel molecular mechanism of anticancer activity of ActD as an oncogenic c-Myc promoter G-quadruplex binder. ActD selectively inhibits the elongation of oligonucleotides containing c-Myc promoter G-quadruplex sequence in PCR-stop assays. UV-vis spectroscopic and circular dichroism studies suggest that ActD interacts with c-Myc promoter G-quadruplex via a surface end stacking interaction, inducing a mixed-type conformation of the G-quadruplex. ActD selectively inhibits the cellular growth and synthesis of c-Myc mRNA in Ramos cells having the NHEIII(1) region in the translocated c-Myc gene. In addition, the results of promoter assays using two kinds of NHEIII(1) region mutants and wild-type constructs strongly support the idea that binding of ActD with G-quadruplex formed in the promoter region results in the reporter gene being turned off. Our study reveals a novel mechanism underlying the anticancer activity of ActD, whereby ActD interacts with oncogenic promoter G-quadruplex DNA to repress gene expression.},
number = {31},
journal = {Biochemistry},
author = {Kang, Hyun-Jin and Park, Hyun-Ju},
month = aug,
year = {2009},
pmid = {19496619},
keywords = {\#nosource, Antibiotics, Antineoplastic, Antineoplastic: chemistry, Antineoplastic: metabolism, Antineoplastic: toxicity, Binding Sites, Cell Line, Cell Proliferation, Cell Proliferation: drug effects, DNA, Dactinomycin, Dactinomycin: chemistry, Dactinomycin: metabolism, Dactinomycin: toxicity, G-Quadruplexes, Genetic, Humans, Neoplasm, Neoplasm: chemistry, Neoplasm: metabolism, Oncogenes, Promoter Regions, Proto-Oncogene Proteins c-myc, Proto-Oncogene Proteins c-myc: antagonists \& inhib, Proto-Oncogene Proteins c-myc: chemistry, Proto-Oncogene Proteins c-myc: genetics, Transcription, Tumor},
pages = {7392--8},
}
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UV-vis spectroscopic and circular dichroism studies suggest that ActD interacts with c-Myc promoter G-quadruplex via a surface end stacking interaction, inducing a mixed-type conformation of the G-quadruplex. ActD selectively inhibits the cellular growth and synthesis of c-Myc mRNA in Ramos cells having the NHEIII(1) region in the translocated c-Myc gene. In addition, the results of promoter assays using two kinds of NHEIII(1) region mutants and wild-type constructs strongly support the idea that binding of ActD with G-quadruplex formed in the promoter region results in the reporter gene being turned off. 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