IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL.

Détails

ID Serval
serval:BIB_75DB9068E081
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL.
Périodique
Blood
Auteur(s)
Nogai H., Wenzel S.S., Hailfinger S., Grau M., Kaergel E., Seitz V., Wollert-Wulf B., Pfeifer M., Wolf A., Frick M., Dietze K., Madle H., Tzankov A., Hummel M., Dörken B., Scheidereit C., Janz M., Lenz P., Thome M., Lenz G.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
2013
Volume
122
Numéro
13
Pages
2242-2250
Langue
anglais
Résumé
Constitutive activation of the nuclear factor-κ B (NF-κB) pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Recurrent mutations of NF-κB regulators that cause constitutive activity of this oncogenic pathway have been identified. However, it remains unclear how specific target genes are regulated. We identified the atypical nuclear IκB protein IκB-ζ to be upregulated in ABC compared with germinal center B-cell-like (GCB) DLBCL primary patient samples. Knockdown of IκB-ζ by RNA interference was toxic to ABC but not to GCB DLBCL cell lines. Gene expression profiling after IκB-ζ knockdown demonstrated a significant downregulation of a large number of known NF-κB target genes, indicating an essential role of IκB-ζ in regulating a specific set of NF-κB target genes. To further investigate how IκB-ζ mediates NF-κB activity, we performed immunoprecipitations and detected a physical interaction of IκB-ζ with both p50 and p52 NF-κB subunits, indicating that IκB-ζ interacts with components of both the canonical and the noncanonical NF-κB pathway in ABC DLBCL. Collectively, our data demonstrate that IκB-ζ is essential for nuclear NF-κB activity in ABC DLBCL, and thus might represent a promising molecular target for future therapies.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/11/2013 10:22
Dernière modification de la notice
08/05/2019 20:31
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