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Poster (Scientific congresses and symposiums)
Promoter specific regulation of NF-kappaB by RelA phosphorylation on Ser547
Trussart, Charlotte; Orban, Tanguy; Di Valentin, Emmanuel et al.
2014Discobel meeting
 

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Keywords :
NF-kappaB; TNF
Abstract :
[en] NF-KB (p50/RelA) controls the expression of numerous genes involved in inflammation, survival, proliferation, and cancer initiation and progression. Both classical NF-kB activation by pro-inflammatory cytokines and ATM-dependant activation by DNA damage require IKK activation and IkBa degradation. Stimuli dependant phosphorylation of p65 controls its transcriptional potential often in a gene specific manner. Previously, we have reported a direct interaction between RelA and ATM, and, demonstrated the in vitro phosphorylation of Ser547 by this kinase. A comparative transcriptomic analysis performed in HEK cells expressing either p65WT or p65S547A identified several differentially transcribed genes after an etoposide treatment. Substitution of S547 to alanine does not affect p65 binding on the kB site of the modulated promoters but it reduces p65 interaction with HDAC1. The resulting enhanced histone H3 acetylation increases gene transcription at some specific promoters. Our data indicate that ATM regulates a sub-set of NF-kB dependent genes after a genotoxic stress by direct phosphorylation of p65. Presently, we are investigating the impact of p65S547A/D mutations after the addition of TNFa in Mefs p65 KO complemented with HA-p65WT or S547A/D. No differences are observed in the degradation of IkBb or the nuclear translocation of p50/p65. However both basal and TNFa-induced transcription levels of some kB dependent genes are elevated in Mefs expressing p65S547D. The role of ATM in NF-kB activation by TNFa is analyzed.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Trussart, Charlotte ;  Université de Liège - ULiège > Doct. sc. (bioch., biol. mol.&cell., bioinf.&mod.-Bologne)
Orban, Tanguy ;  Université de Liège - ULiège
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie
Habraken, Yvette ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Language :
English
Title :
Promoter specific regulation of NF-kappaB by RelA phosphorylation on Ser547
Publication date :
29 August 2014
Event name :
Discobel meeting
Event organizer :
WIV-ISP
Event date :
29 aout 2014
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
ULiège - Université de Liège [BE]
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since 19 November 2014

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