糖原合成酶激酶3介导的BCL-3磷酸化调节其降解及其致癌性。
GSK3-mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity.
作者信息
Viatour Patrick, Dejardin Emmanuel, Warnier Michael, Lair Florence, Claudio Estefania, Bureau Fabrice, Marine Jean-Christophe, Merville Marie-Paule, Maurer Ulrich, Green Douglas, Piette Jacques, Siebenlist Ulrich, Bours Vincent, Chariot Alain
机构信息
Laboratory of Medical Chemistry and Human Genetics, Liège, Belgium.
出版信息
Mol Cell. 2004 Oct 8;16(1):35-45. doi: 10.1016/j.molcel.2004.09.004.
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 Cxcl1. Our results therefore suggest that constitutive BCL-3 phosphorylation by GSK3 regulates BCL-3 turnover and transcriptional activity.
癌蛋白BCL-3是一种核转录因子，它通过与p50或p52形成异源复合物来激活核因子-κB（NF-κB）靶基因。BCL-3在体内会发生磷酸化，但迄今为止尚未鉴定出特异性的BCL-3激酶。在本报告中，我们表明BCL-3是蛋白激酶GSK3的底物，并且由Akt激活所抑制的GSK3介导的BCL-3磷酸化通过蛋白酶体途径靶向其降解。这种磷酸化调节其与组蛋白去乙酰化酶1、3和6的结合，并通过选择性控制新鉴定的靶基因子集（如分泌性白细胞蛋白酶抑制剂（SLPI）和趋化因子Cxcl1）的表达来减弱其致癌性。因此，我们的结果表明，GSK3对BCL-3的组成型磷酸化调节BCL-3的周转和转录活性。
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