GSK3-Mediated BCL-3 Phosphorylation Modulates Its Degradation and Its Oncogenicity
- 作者：Patrick Viatour ; Emmanuel Dejardin ; Michael Warnier ; Florence Lair ; Estefania Claudio ; Fabrice Bureau ; Jean-Christophe Marine ; Marie-Paule Merville ; Ulrich Maurer ; Douglas Green et al.
- 刊名：Molecular Cell
- 出版年：2004
- 期刊代码：111_10972765
- 类别：bio
- 出版时间：8 October 2004
- 卷：16
- 期：1
- 页码：35-45
- 文件大小：492 K
摘要
The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-κB 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 Cxcl1. Our results therefore suggest that constitutive BCL-3 phosphorylation by GSK3 regulates BCL-3 turnover and transcriptional activity.