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Title
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Histone deacetylase inhibitor trichostatin A sustains sodium pervanadate-induced NF-kappa B activation by delaying I kappa B alpha mRNA resynthesis - Comparison with tumor necrosis factor alpha
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Author
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Abstract
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| NF-kappa B 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-kappa B activation and delays I kappa B alpha cytoplasmic reappearance. Here, we demonstrated that TSA also prolongs NF-kappa B activation when induced by the insulino-mimetic pervanadate (PV), a tyrosine phosphatase inhibitor that initiates an atypical NF-kappa B signaling. This extension is similarly correlated with delayed I kappa B alpha cytoplasmic reappearance. However, whereas TSA causes a prolonged IKK activity when added to TNF alpha, it does not when added to PV. Instead, quantitative reverse transcriptase-PCR revealed a decrease of i kappa b alpha mRNA level after TSA addition to PV stimulation. This synthesis deficit of the inhibitor could explain the sustained NF-kappa B residence in the nucleus. In vivo analysis by chromatin immunoprecipitation assays uncovered that, for PV induction but not for TNF alpha, the presence of TSA provokes several impairments on the i kappa b alpha promoter: (i) diminution of RNA Pol II recruitment; (ii) reduced acetylation and phosphorylation of histone H3-Lys(14) and -Ser(10), respectively; (iii) decreased presence of phosphorylated p65-Ser536; and (iv) reduction of IKK alpha binding. The recruitment of these proteins on the icam-1 promoter, another NF-kappa B-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-kappa B pathway and the targeted promoter in question. This indicates that one overall histone deacetylase role is to inhibit NF-kappa B activation by molecular mechanisms specific of the stimulus and the promoter. |
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Language
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English
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Source (journal)
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Journal of biological chemistry. - Baltimore, Md
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Publication
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Baltimore, Md
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2007
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ISSN
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0021-9258
[print]
1083-351X
[online]
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DOI
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10.1074/JBC.M609166200
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Volume/pages
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282
:21
(2007)
, p. 15383-15393
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ISI
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000246589600014
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Full text (Publisher's DOI)
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