Abstract
The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associates with the molecular chaperone HSP90 in the cytoplasm. There are a few reports about the association or dissociation of AhR and HSP90, and which domain of HSP90 binds to AhR. We reported the association and activation mechanisms between HSP90 and AhR-PAS or AhR-bHLH. In the current study, we found that cisplatin inhibits the AhR activation. Although ATP and 17-DMAG have no effect on the dissociation of HSP90 from AhR, some contents of HSP90 were dissociated from AhR in the presence of cisplatin. We could detect the increase of CYP1A in the presence of 3-MC. On the contrary, the induction of CYP1A1 was inhibited in the presence of cisplatin. We couldn’t detect AhR in the HeLa cell soluble fraction in the presence of 50 μM cisplatin. In the presence of MG-132, we could detect AhR. These results suggested that AhR was dissociated from the HSP90 chaperone complex and processed during the protein proteasome degradation system in the presence of cisplatin.
Highlights
The molecular chaperone 90-kDa of heat shock protein (HSP90) is an essential protein in eukaryotic cells
We investigated the influence of cisplatin on the association or dissociation of aryl hydrocarbon receptor (AhR) from HSP90-cochaperone complex
For the glutathione S-transferase (GST) pull-down assay, the concentration of ATP, 17-DMAG, and cisplatin were according to previous reports [9] [10]. 2.5 μM GST-basic helix-loop-helix (bHLH) or GSTAhR-ΔAD or GST protein was added to a solution of 2.5 μM HSP90 in the presence or absence of 3 μM 3MC, 50 μM cisplatin, 50 μM 17-DMAG, 1 mM ATP and 150 μl buffer A (0.1 M KCl, 10 mM MgCl2, 20 mM Na2MoO4, 0.6 M NaCl, 5% Glycerol, 0.1% NP-40 in 25 mM HEPES-KOH pH 7.4)
Summary
The molecular chaperone HSP90 is an essential protein in eukaryotic cells. It interacts with more than 300 proteins, and regulates the physiological function in the cell [1] [2]. HSP90 interacts with a cancer, and the inhibitor of HSP90 is ex-
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