The Repressing Function of the Oncoprotein BCL-3 Requires CtBP, while Its Polyubiquitination and Degradation Involve the E3 Ligase TBLR1
The Repressing Function of the Oncoprotein BCL-3 Requires CtBP, while Its Polyubiquitination and Degradation Involve the E3 Ligase TBLR1
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DOI：
10.1128/mcb.01600-09
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发表时间：
2010-08-01
影响因子：
5.3
通讯作者：
Chariot, Alain
中科院分区：
文献类型：
--
作者：
Keutgens, Aurore;Shostak, Kateryna;Chariot, Alain
核和致癌的bcl3蛋白与核因子-kappaB蛋白p50和p52结合后激活或抑制基因转录，但与bcl3特异性相互作用并驱动bcl3介导的基因表达效应的分子在很大程度上仍未确定。此外，GSK3介导的bcl3的磷酸化通过蛋白酶体启动其降解，但参与这一降解途径的蛋白质的特性很差。BCL-3相互作用伙伴的生化纯化导致CtBP被鉴定为BCL-3抑制基因转录能力所必需的分子。在角质形成细胞中，cTBP对于bcl3的致癌潜能和抑制紫外线诱导的细胞凋亡的能力也是必需的。我们还将E3连接酶TBLR1定义为通过不依赖GSK3的途径参与bcl3降解的蛋白质。因此，我们的数据表明，LSD1/CtBP复合体是致癌I kappa B蛋白抑制能力所必需的，并且它们在E3连接酶TBLR1和NF-kappa B之间建立了功能联系。
The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kappa B proteins p50 and p52, yet the molecules that specifically interact with BCL-3 and drive BCL-3-mediated effects on gene expression remain largely uncharacterized. Moreover, GSK3-mediated phosphorylation of BCL-3 triggers its degradation through the proteasome, but the proteins involved in this degradative pathway are poorly characterized. Biochemical purification of interacting partners of BCL-3 led to the identification of CtBP as a molecule required for the ability of BCL-3 to repress gene transcription. CtBP is also required for the oncogenic potential of BCL-3 and for its ability to inhibit UV-mediated cell apoptosis in keratinocytes. We also defined the E3 ligase TBLR1 as a protein involved in BCL-3 degradation through a GSK3-independent pathway. Thus, our data demonstrate that the LSD1/CtBP complex is required for the repressing abilities of an oncogenic I kappa B protein, and they establish a functional link between the E3 ligase TBLR1 and NF-kappa B.