The transcription factor FOXM1 is a cellular target of the natural product thiostrepton
Author: ["Nagaratna S. Hegde","Deborah A. Sanders","Raphaël Rodriguez","Shankar Balasubramanian"]
Publication: Nature Chemistry
CITE.CC academic search helps you expand the influence of your papers.
Abstract
Transcription factors are proteins that bind specifically to defined DNA sequences to promote gene expression. Targeting transcription factors with small molecules to modulate the expression of certain genes has been notoriously difficult to achieve. The natural product thiostrepton is known to reduce the transcriptional activity of FOXM1, a transcription factor involved in tumorigenesis and cancer progression. Herein we demonstrate that thiostrepton interacts directly with FOXM1 protein in the human breast cancer cells MCF-7. Biophysical analyses of the thiostrepton–FOXM1 interaction provide additional insights on the molecular mode of action of thiostrepton. In cellular experiments, we show that thiostrepton can inhibit the binding of FOXM1 to genomic target sites. These findings illustrate the potential druggability of transcription factors and provide a molecular basis for targeting the FOXM1 family with small molecules. The natural product thiostrepton is known to have anticancer properties but its mechanism of action is not known. Here, it is shown that thiostrepton binds to the protein FOXM1, preventing its interaction with several gene promoters and inhibits their expression. This illustrates the druggability of transcription factors, and provides a molecular basis for targeting FOXM1.
Cite this article
Hegde, N., Sanders, D., Rodriguez, R. et al. The transcription factor FOXM1 is a cellular target of the natural product thiostrepton. Nature Chem 3, 725–731 (2011). https://doi.org/10.1038/nchem.1114
