The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication.
(2014) In Chemico-Biological Interactions 214(Mar 11). p.69-76- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4383220
- author
- Pérez, Moisés ; Soler-Torronteras, Rafael ; Collado, Juan A ; Limones, Carmen G ; Hellsten, Rebecka LU ; Johansson, Martin H LU ; Sterner, Olov ; Bjartell, Anders LU ; Calzado, Marco A and Muñoz, Eduardo
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Chemico-Biological Interactions
- volume
- 214
- issue
- Mar 11
- pages
- 69 - 76
- publisher
- Elsevier
- external identifiers
-
- pmid:24631022
- wos:000335705800009
- scopus:84896475169
- pmid:24631022
- ISSN
- 1872-7786
- DOI
- 10.1016/j.cbi.2014.02.012
- language
- English
- LU publication?
- yes
- id
- 69090608-f13c-47a1-a7d3-77544d5eed44 (old id 4383220)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24631022?dopt=Abstract
- date added to LUP
- 2016-04-01 09:53:37
- date last changed
- 2022-02-09 20:42:38
@article{69090608-f13c-47a1-a7d3-77544d5eed44, 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.}}, author = {{Pérez, Moisés and Soler-Torronteras, Rafael and Collado, Juan A and Limones, Carmen G and Hellsten, Rebecka and Johansson, Martin H and Sterner, Olov and Bjartell, Anders and Calzado, Marco A and Muñoz, Eduardo}}, issn = {{1872-7786}}, language = {{eng}}, number = {{Mar 11}}, pages = {{69--76}}, publisher = {{Elsevier}}, series = {{Chemico-Biological Interactions}}, title = {{The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication.}}, url = {{http://dx.doi.org/10.1016/j.cbi.2014.02.012}}, doi = {{10.1016/j.cbi.2014.02.012}}, volume = {{214}}, year = {{2014}}, }