Reference : Histone deacetylase inhibitor trichostatin A sustains sodium pervanadate-induced NF-k...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Histone deacetylase inhibitor trichostatin A sustains sodium pervanadate-induced NF-kappa B activation by delaying IkappaBalpha mRNA resynthesis : comparison with tumor necrosis factor alpha
Horion, Julie mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Gloire, Geoffrey mailto [Université de Liège - ULiège > > GIGA-R : Virologie - Immunologie >]
El Mjiyad, Nadia mailto [> >]
Quivy, Vincent [> >]
Vermeulen, Linda [> >]
Vanden Berghe, Wim [> >]
Haegeman, Guy [> >]
Van Lint, Carine [> >]
Piette, Jacques mailto [Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research >]
Habraken, Yvette mailto [Université de Liège - ULiège > > GIGA-R : Virologie - Immunologie >]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBi)
[en] Trichostatin A ; IkappaBalpha ; pervanadate ; IKKalpha
[en] NF-kappaB is a crucial transcription factor tightly regulated by protein
interactions and post-translational modifications, like phosphorylation
and acetylation. A previous study has shown that trichostatin
A (TSA), a histone deacetylase inhibitor, potentiates
tumor necrosis factor (TNF) alpha-elicited NF-kappaB activation and
delays IkappaBalpha cytoplasmic reappearance. Here, we demonstrated
that TSA also prolongs NF-kappaB activation when induced by the
insulino-mimetic pervanadate (PV), a tyrosine phosphatase inhibitor
that initiates an atypical NF-kappaB signaling. This extension is
similarly correlated with delayed IkappaBalpha cytoplasmic reappearance.
However, whereas TSA causes a prolonged IKK activity when
addedtoTNFalpha, it does notwhenaddedtoPV.Instead, quantitative
reverse transcriptase-PCR revealed a decrease of ikappabalphamRNAlevel
after TSA addition to PV stimulation. This synthesis deficit of the
inhibitor could explain the sustained NF-kappaB residence in the
nucleus. In vivo analysis by chromatin immunoprecipitation assays
uncovered that, forPVinduction but not forTNFalpha, the presence of
TSA provokes several impairments on the ikappabalphapromoter: (i) diminution
of RNA Pol II recruitment; (ii) reduced acetylation and
phosphorylation of histone H3-Lys14 and -Ser10, respectively; (iii)
decreased presence of phosphorylated p65-Ser536; and (iv) reduction
of IKKalphabinding. The recruitment of these proteins on the
icam-1 promoter, another NF-kappaB-regulated gene, is not equally
affected, suggesting a promoter specificity of PV with TSA stimulation.
Taken together, these data suggest that TSA acts differently
depending on the NF-kappaB pathway and the targeted promoter in
question. This indicates that one overall histone deacetylase role is
to inhibit NF-kappaB activation by molecular mechanisms specific of
the stimulus and the promoter.
Giga-Signal Transduction
Université de Liège - FNRS
Modulation de l'activation du NF-kappaB par un inhibiteur d'histone désacétylase

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