Reference : Phosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/127093
Phosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
English
[en] Phosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Sabatel, Hélène [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Di Valentin, Emmanuel mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie et immunologie >]
Gloire, Geoffrey mailto [Université de Liège - ULg > > Interface Entreprises-Université >]
Dequiedt, Franck mailto [Université de Liège - ULg > > GIGA-Research >]
Piette, Jacques mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie - Immunologie >]
Habraken, Yvette mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
8-Jun-2012
PLoS ONE
Public Library of Science
Yes (verified by ORBi)
International
1932-6203
San Franscisco
CA
[en] ATM ; p65 ; NF-kappaB
[en] The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65.
Université de Liège, GIGA-R, Virology Immunology Unit
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS, TELEVIE, Federal Scientific Policy PAI6/18, “Centre anticancéreux auprès de l’ULg”
Phosphorylation de la sous-unité p65 du facteur de transcription nucléaire kappaB par la kinase "Ataxia Telangiectasia Mutated protein".
http://hdl.handle.net/2268/127093
10.1371/journal.pone.0038246
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0038246

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