Open AccessActinomycin D specifically inhibits the interaction between transcription factor Sp1 and its binding site.
Author(s) -
Małgorzata Czyż,
Marek Gniazdowski
Publication year - 1998
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1998_4319
Subject(s) - dna , transcription factor , binding site , dna binding protein , transcription (linguistics) , dactinomycin , umbilical vein , mechanism of action , nuclear protein , plasma protein binding , electrophoretic mobility shift assay , dna binding site , microbiology and biotechnology , biology , chemistry , promoter , biochemistry , protein biosynthesis , gene , gene expression , in vitro , linguistics , philosophy , cycloheximide
The mode of action of many anticancer drugs involves DNA interactions. We here examine the ability of actinomycin D to alter the specific binding of transcription factors Spl and NFkappaB to their DNA sequences. Employing an electrophoretic mobility shift assay, it is shown that actinomycin D inhibits complex formation between nuclear proteins present 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 importance 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 with the NFkappaB binding site. The results support the view that DNA-binding drugs displaying high sequence-selectivity can exhibit distinct effects on the interaction between DNA and different DNA-binding proteins.