M. Czyz et M. Gniazdowski, ACTINOMYCIN-D SPECIFICALLY INHIBITS THE INTERACTION BETWEEN TRANSCRIPTION FACTOR SP1 AND ITS BINDING-SITE, Acta Biochimica Polonica, 45(1), 1998, pp. 67-73
The mode of action of many anticancer drugs involves DNA interactions.
We here examine the ability of actinomycin D to alter the specific bi
nding of transcription factors Sp1 and NF kappa B to their DNA sequenc
es. Employing an electrophoretic mobility shift assay, it is shown tha
t actinomycin D inhibits complex formation between nuclear proteins pr
esent in the extracts from stimulated human umbilical vein endothelial
cells and the Sp1-binding site. Actinomycin D is also able to induce
disruption of preformed DNA-protein complexes, pointing to the importa
nce of an equilibrium of three components: actinomycin D, protein and
DNA for drug action. The effect of actinomycin D is sequence-specific,
since no inhibition is observed for interaction of nuclear proteins w
ith the NF kappa B binding site. The results support the view that DNA
-binding drugs displaying high sequence-selectivity can exhibit distin
ct effects on the interaction between DNA and different DNA-binding pr
oteins.