1. The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication.
- Author
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Pérez M, Soler-Torronteras R, Collado JA, Limones CG, Hellsten R, Johansson M, Sterner O, Bjartell A, Calzado MA, and Muñoz E
- Subjects
- Cell Line, Tumor, Cell Nucleus metabolism, Humans, Lactones isolation & purification, alpha Karyopherins metabolism, Ascomycota chemistry, Biological Transport drug effects, Cell Nucleus drug effects, HIV-1 physiology, Lactones pharmacology, NF-kappa B metabolism, Virus Replication drug effects
- Abstract
Galiellalactone (GL) is a metabolite produced by the fungus Galiella rufa that presents antitumor and immunomodulatory activities. GL interferes with the binding to DNA of signal transducer and activator of transcription (STAT)-3 and also inhibits other signal pathways such as NF-κB, but the mechanism of action in this pathway remains unknown. In this study we report that GL inhibits vesicular stomatitis virus-recombinant HIV-1 infection and the NF-κB-dependent transcriptional activity of the HIV-LTR promoter. We found that GL prevents the binding of NF-κB to DNA but neither affects the phosphorylation and degradation of NF-κB inhibitory protein, IκBα, nor the phosphorylation and acetylation of the NF-κB p65 subunit. However, GL prevents the association of p65 with the importin α3 impairing the nuclear translocation of this transcription factor. Using a biotinylated probe we found that GL binds to p65 but not to importin α3. Therefore, GL is a dual NF-κB/STAT3 inhibitor that could serve as a lead compound for the development of novel drugs against HIV-1, cancer and inflammatory diseases., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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