GSK3-Mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity

[en] The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-kappaB target genes through formation of heterocomplexes with p50 or p52. BCL-3 is phosphorylated in vivo, but specific BCL-3 kinases have not been identified so far. In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with HDAC1, -3, and -6 and attenuates its oncogenicity by selectively controlling the expression of a subset of newly identified target genes such as SLPI and CxcI1. Our results therefore suggest that constitutive BCL-3 phosphorylation by GSK3 regulates BCL-3 turnover and transcriptional activity.

Research Center/Unit :

GIGA‐R - Giga‐Research - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Viatour, Patrick ; Université de Liège - ULiège > Chimie médicale

Dejardin, Emmanuel ; Université de Liège - ULiège > Virologie - Immunologie

Warnier, Michael

Lair, Florence

Claudio, Estefania

Bureau, Fabrice ; Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie et biologie moléculaire

Marine, Jean Christophe

Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Maurer, Ulrich

Green, Douglas

More authors (4 more)

Language :

English

Title :

GSK3-Mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity

Publication date :

08 October 2004

Journal title :

Molecular Cell

ISSN :

1097-2765

eISSN :

1097-4164

Publisher :

Cell Press, Cambridge, United Kingdom

Volume :

Issue :

Pages :

35-45

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

Insight into the oncogenic potential of BCL-3

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique
Télévie
FBC
ULg. ARC - Université de Liège. Actions de Recherche Concertées

Available on ORBi :

since 06 January 2009

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