The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication.
Author
Summary, in English
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.
Department/s
- Urological cancer, Malmö
- Medical Protein Science
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- EpiHealth: Epidemiology for Health
Publishing year
2014
Language
English
Pages
69-76
Publication/Series
Chemico-Biological Interactions
Volume
214
Issue
Mar 11
Links
Document type
Journal article
Publisher
Elsevier
Topic
- Biochemistry and Molecular Biology
Status
Published
Research group
- Urological cancer, Malmö
- Medical Protein Science
ISBN/ISSN/Other
- ISSN: 1872-7786