Article (Scientific journals)
Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes.
Robert, Isabelle; Aussems, Marie; Keutgens, Aurore et al.
2009In Oncogene, 28 (13), p. 1626-1638
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Keywords :
NF-kappa B; lymphome; p52
Abstract :
[en] Constitutive nuclear factor (NF)-kappaB activation in haematological malignancies is caused in several cases by loss of function mutations within the coding sequence of NF-kappaB inhibitory molecules such as IkappaBalpha or p100. Hut-78, a truncated form of p100, constitutively generates p52 and contributes to the development of T-cell lymphomas but the molecular mechanism underlying this oncogenic potential remains unclear. We show here that MMP9 gene expression is induced through the alternative NF-kappaB-activating pathway in fibroblasts and also on Hut-78 or p52 overexpression in fibroblasts as well as in lymphoma cells. p52 is critical for Hut-78-mediated MMP9 gene induction as a Hut-78 mutant as well as other truncated NF-kappaB2 proteins that are not processed into p52 failed to induce the expression of this metalloproteinase. Conversely, MMP9 gene expression is impaired in p52-depleted HUT-78 cells. Interestingly, MLL1 and MLL2 H3K4 methyltransferase complexes are tethered by p52 on the MMP9 but not on the IkappaBalpha promoter, and the H3K4 trimethyltransferase activity recruited on the MMP9 promoter is impaired in p52-depleted HUT-78 cells. Moreover, MLL1 and MLL2 are associated with Hut-78 in a native chromatin-enriched extract. Thus, we identified a molecular mechanism by which the recruitment of a H3K4 histone methyltransferase complex on the promoter of a NF-kappaB-dependent gene induces its expression and potentially the invasive potential of lymphoma cells harbouring constitutive activity of the alternative NF-kappaB-activating pathway.
Research center :
Giga-Signal Transduction, GIGA-R
Disciplines :
Biochemistry, biophysics & molecular biology
Hematology
Author, co-author :
Robert, Isabelle ;  Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale
Aussems, Marie ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Keutgens, Aurore ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Zhang-Shao, Xin ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Hennuy, Benoît ;  Université de Liège - ULiège > GIGA-Management : Plate-forme transcriptomique
Viatour, Patrick ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Vanstraelen, Gaetan
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Chapelle, Jean-Paul ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
de Leval, Laurence ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Département des sciences biomédicales et précliniques
Dejardin, Emmanuel ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Gothot, André ;  Université de Liège - ULiège > Hématologie biologique et immuno hématologie
Chariot, Alain ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
More authors (4 more) Less
Language :
English
Title :
Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes.
Publication date :
02 April 2009
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
Volume :
28
Issue :
13
Pages :
1626-1638
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Caractérisation des propriétés oncogéniques des protéines NF-kB/IkBs
Funders :
Fondation contre le Cancer [BE]
Télévie [BE]
Fonds Léon Fredericq [BE]
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