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

被引：113

作者：

Viatour, P

Dejardin, E

Warnier, M

Lair, F

Claudio, E

Bureau, F

Marine, JC

Merville, MP

Maurer, U

Green, D

Piette, J

Siebenlist, U

Bours, V

Chariot, A ^{[1
]}

机构：

[1] Univ Liege, Lab Med Chem & Human Genet, B-4000 Liege, Belgium

[2] Univ Liege, Dept Physiol, B-4000 Liege, Belgium

[3] Univ Liege, Lab Virol & Immunol, Ctr Biomed Integrated Genoproteom, B-4000 Liege, Belgium

[4] La Jolla Inst Allergy & Immunol, Div Cellular Immunol, San Diego, CA 92121 USA

[5] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[6] Flanders Interuniv Inst BIotechnol, Lab Mol Canc Biol, Ghent, Belgium

来源：

MOLECULAR CELL | 2004年 / 16卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

D O I：

10.1016/j.molcel.2004.09.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：35 / 45

页数：11

共 32 条

[1] Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-κB and β-amyloid precursor protein [J].