Transcriptional Regulation by Gold(I) Thiolates Involving Interaction with Conserved Cysteine Residues in the Photo-Oncogene Products Jun and Fos
How Gold Compounds Affect DNA Binding in Cancer Proteins
publication
Author Information
Author(s): Malcolm L. Handel, Colin K. W. Watts, Richard O. Day, Robert L. Sutherland
Primary Institution: Garvan Institute of Medical Research
Hypothesis
Gold(I) salts inhibit AP-1 DNA binding by forming complexes with cysteine residues.
Conclusion
Gold(I) thiolates inhibit AP-1 DNA binding in vitro and reduce AP-1 mediated transcription in living cells.
Supporting Evidence
- Gold(I) thiolates inhibited AP-1 DNA binding with an IC50 of 3 i.dVl.
- Inhibition was virtually complete with 10 IM gold(I).
- Recombinant Jun and Fos proteins with cysteine to serine mutations were resistant to gold(I) thiolates.
- AP-1 mediated transcription was significantly inhibited by 10 IM gold(I) thiomalate in MCF-7 cells.
Takeaway
Gold compounds can stop certain proteins in our cells from binding to DNA, which might help explain how they work in cancer treatment.
Methodology
Crude nuclear extracts were treated with gold(I) thiolates, and DNA binding was assessed using electrophoretic mobility shift analysis.
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