Sp1 transcription factor as a target for anthracyclines: effects on gene transcription.

@article{Mansilla2008Sp1TF,
  title={Sp1 transcription factor as a target for anthracyclines: effects on gene transcription.},
  author={Sylvia Mansilla and Jos{\'e} Portugal},
  journal={Biochimie},
  year={2008},
  volume={90 7},
  pages={
          976-87
        }
}
The analysis of how anthracyclines interfere with DNA-protein complexes, and the evaluation of their effects on gene transcription, can promote the development of new more specific anti-tumour agents. Daunorubicin and the bisintercalating anthracycline WP631 (which binds more tightly to DNA) have been compared for their ability to inhibit Sp1-DNA interactions and gene transcription. WP631 is more efficient at inhibiting transcription initiation from promoters containing an Sp1-binding site, and… Expand
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References

SHOWING 1-10 OF 69 REFERENCES
Analysis of the effects of daunorubicin and WP631 on transcription.
TLDR
The resulting data suggest that WP631 might circumvent some kinds of tumor resistance at rather low drug concentrations, inhibit c-myc expression in some cell lines, and exert its antitumoral effect by inducing apoptosis. Expand
Sp1-targeted inhibition of gene transcription by WP631 in transfected lymphocytes.
TLDR
This work tested whether the Sp3 protein, whose putative binding sequence overlaps the Sp1 site, can inhibit Sp1-activated transcription and interfere with drug-DNA interactions. Expand
Bisanthracycline WP631 inhibits basal and Sp1-activated transcription initiation in vitro.
TLDR
WP631 was around 15 times more efficient at inhibiting transcription initiation when used with an adenovirus promoter containing an upstream Sp1-protein binding site under experimental conditions in which the Sp1 protein acted as a transactivator in vitro. Expand
Transcription factors as targets for DNA-interacting drugs.
TLDR
This review has summarized recent advances which have been made towards understanding the mechanisms by which small molecules interfere with the function of transcription factors. Expand
A comparison of DNA-binding drugs as inhibitors of E2F1- and Sp1-DNA complexes and associated gene expression.
TLDR
Time course transcription in a cell-free assay with addition of various drug concentrations indicated that high drug concentrations of either mitoxantrone or distamycin completely blocked transcription, while low drug concentrations could delay the synthesis of transcripts. Expand
Promoter-specific inhibition of transcription by daunorubicin in Saccharomyces cerevisiae.
TLDR
It is proposed that daunorubicin and some transcription factors compete for DNA sequences encompassing CpG steps, and that this is the main determinant of the effects of the drug on transcription in vivo. Expand
Modulation of DNA-protein interactions in the P1 and P2 c-myc promoters by two intercalating drugs.
TLDR
Run-off transcription experiments in vitro showed that the effect of elsamicin A on Sp1 binding is followed by the maintenance or a relative rise in transcription levels from the P1 promoter of c-myc, while actinomycin D always inhibited the transcription from theP1 c- myc promoter in a concentration-dependent manner. Expand
A bisanthracycline (WP631) represses uPAR gene expression and cell migration of RKO colon cancer cells by interfering with transcription factor binding to a chromatin-accessible -148/-124 promoter region.
TLDR
It is shown that the chromatinized -148/-124 regulatory region of the uPAR promoter is accessible to small molecules and that WP631, which disrupts the interaction of DNA binding proteins with this region, diminishes uPAR expression and function. Expand
Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo.
TLDR
Mithramycin treatment of MCF-7 human breast carcinoma cells containing an amplified DHFR gene induces selective inhibition of DHFR transcription initiation, resulting in a decline in DHFR mRNA level and enzyme activity, suggesting that it is possible to modulate the overexpression of theDHFR gene in methotrexate resistant cells. Expand
Distamycin A and tallimustine inhibit TBP binding and basal in vitro transcription.
TLDR
A functional in vitro model will provide a way to investigate the activity of sequence-specific DNA binding drugs with potential anti-viral and anti-tumour activity and to develop novel more selective compounds. Expand
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