Article (Scientific journals)
Phosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Sabatel, Hélène; Di Valentin, Emmanuel; Gloire, Geoffrey et al.
2012In PLoS ONE
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Keywords :
ATM; p65; NF-kappaB
Abstract :
[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.
Research center :
Université de Liège, GIGA-R, Virology Immunology Unit
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Sabatel, Hélène ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Gloire, Geoffrey ;  Université de Liège - ULiège > Interface Entreprises-Université
Dequiedt, Franck  ;  Université de Liège - ULiège > GIGA-Research
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 :
Phosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Alternative titles :
[en] Phosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Publication date :
2012
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Phosphorylation de la sous-unité p65 du facteur de transcription nucléaire kappaB par la kinase "Ataxia Telangiectasia Mutated protein".
PAI 6/18
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
CAC - Centre anticancéreux près l'Université de Liège asbl [BE]
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