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The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication.

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 (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)
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author
organization
publishing date
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
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
2014-04-03 15:20:44
date last changed
2017-06-25 03:02:03
@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},
  volume       = {214},
  year         = {2014},
}