Reference : Potentiation of tumor necrosis factor-induced NF-kappa B activation by deacetylase in...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/3752
Potentiation of tumor necrosis factor-induced NF-kappa B activation by deacetylase inhibitors is associated with a delayed cytoplasmic reappearance of I kappa B alpha
English
Adam, Emmanuelle [> > > >]
Quivy, Vincent [> > > >]
Bex, Françoise [> > > >]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Collette, Yves [> > > >]
Vanhulle, Caroline [> > > >]
Haterte, Stéphanie mailto [Université de Liège - ULg > Département des sciences de la santé publique > Informatique médicale et biostatistique >]
Goffin, Véronique [Centre Hospitalier Universitaire de Liège - CHU > > Dermatopathologie >]
Nguyen, Thi Liên-Anh [> > > >]
Gloire, Geoffrey mailto [Université de Liège - ULg > > Virologie - Immunologie >]
Carrard, Géraldine [> > > >]
Friguet, Bertrand [> > > >]
de Launoit, Yvan [> > > >]
Burny, Arsène [> > > >]
Bours, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Piette, Jacques mailto [Université de Liège - ULg > Département des sciences de la vie > Virologie - Immunologie >]
Van Lint, Carine [> > > >]
Sep-2003
Molecular and Cellular Biology
Amer Soc Microbiology
23
17
6200-6209
Yes (verified by ORBi)
International
0270-7306
Washington
[en] NF kappa B ; HDAC ; TNF
[en] Previous studies have implicated acetylases and deacetylases in regulating the transcriptional activity of NF-kappaB. Here, we show that inhibitors of deacetylases such as trichostatin A (TSA) and sodium butyrate (NaBut) potentiated TNF-induced expression of several natural NF-kappaB-driven promoters. This transcriptional synergism observed between TNF and TSA (or NaBut) required intact kappaB sites in all promoters tested and was biologically relevant as demonstrated by RNase protection on two instances of endogenous NF-kappaB-regulated gene transcription. Importantly, TSA prolonged both TNF-induced DNA-binding activity and the presence of NF-kappaKB in the nucleus. We showed that the p65 subunit of NF-kappaB was acetylated in vivo. However, this acetylation was weak, suggesting that other mechanisms could be implicated in the potentiated binding and transactivation activities of NF-kappaB after TNF plus TSA versus TNF treatment. Western blot and immunofluorescence confocal microscopy experiments revealed a delay in the cytoplasmic reappearance of the IkappaBalpha inhibitor that correlated temporally with the prolonged intranuclear binding and presence of NF-kappaB. This delay was due neither to a defect in IkappaBalpha mRNA production nor to a nuclear retention of IkappaBalpha but was rather due to a persistent proteasome-mediated degradation of IkappaBalpha. A prolongation of IkappaB kinase activity could explain, at least partially, the delayed IkappaBalpha cytoplasmic reappearance observed in presence of TNF plus TSA.
Giga-Signal Transduction
FNRS, TELEVIE
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/3752

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
16. Publication MCB TSA p65.pdfNo commentaryPublisher postprint491.62 kBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.