Reference : Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein inv...
Scientific journals : Article
Human health sciences : Hematology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/12339
Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes.
English
Robert, Isabelle [Centre Hospitalier Universitaire de Liège - CHU > > Chimie médicale >]
Aussems, Marie [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Keutgens, Aurore mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Zhang-Shao, Xin [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Hennuy, Benoît mailto [Université de Liège - ULg > > GIGA-Management : Plate-forme transcriptomique >]
Viatour, Patrick [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Vanstraelen, Gaetan [> >]
Merville, Marie-Paule mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Chapelle, Jean-Paul mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
de Leval, Laurence mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Département des sciences biomédicales et précliniques >]
Lambert, Frédéric [> >]
Dejardin, Emmanuel mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Gothot, André mailto [Université de Liège - ULg > > Hématologie biologique et immuno hématologie >]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
2-Apr-2009
Oncogene
Nature Publishing Group
28
13
1626-1638
Yes (verified by ORBi)
International
0950-9232
1476-5594
Basingstoke
United Kingdom
[en] NF-kappa B ; lymphome ; p52
[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.
Giga-Signal Transduction, GIGA-R
Fédéréation belge contre le cancer, FNRS, TELEVIE, Fonds Léon Frédéricq, PAI, phase VI
Caractérisation des propriétés oncogéniques des protéines NF-kB/IkBs
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/12339

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