KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity
KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity
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DOI：
10.1016/j.bbagrm.2015.08.006
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发表时间：
2015-10-01
影响因子：
4.7
通讯作者：
Rezsohazy, Rene
中科院分区：
文献类型：
--
作者：
Bridoux, Laure;Bergiers, Isabelle;Rezsohazy, Rene
转录因子活性的调节依赖于分子间的相互作用或酶的修饰，从而影响它们与DNA顺式调控序列的相互作用，它们的转录激活或抑制，以及这些蛋白质的稳定性或细胞内分布。关于保守的HOX蛋白家族，到目前为止，已经强调了数量有限的活性调节因子。在一个旨在鉴定与Hoxa2相互作用的蛋白质组的蛋白质组框架内，鉴定了KPC泛素-连接酶复合体的适配蛋白KPC2。在这项工作中，KPC2通过共沉淀和双分子荧光互补分析证实了KPC2是Hoxa2的真正相互作用元件。在功能水平上，KPC2抑制转录活性并诱导Hoxa2的核退出。基因表达分析表明，Kpc2在发育中的小鼠胚胎的限制性区域活跃，这些区域与Hoxa2的表达区域重叠。综上所述，我们的数据支持KPC2通过促进Hoxa2重新定位到细胞质来调节Hoxa2。(C)2015爱思唯尔B.V.保留所有权利。
Regulation of transcription factor activity relies on molecular interactions or enzymatic modifications which influence their interaction with DNA cis-regulatory sequences, their transcriptional activation or repression, and stability or intracellular distribution of these proteins. Regarding the well-conserved Hox protein family, a restricted number of activity regulators have been highlighted thus far. In the framework of a proteome-wide screening aiming at identifying proteins interacting with Hoxa2, KPC2, an adapter protein constitutive of the KPC ubiquitin-ligase complex, was identified. In this work, KPC2 was confirmed as being a genuine interactor of Hoxa2 by co-precipitation and bimolecular fluorescence complementation assays. At functional level, KPC2 diminishes the transcriptional activity and induces the nuclear exit of Hoxa2. Gene expression analyses revealed that Kpc2 is active in restricted areas of the developing mouse embryo which overlap with the Hoxa2 expression domain. Together, our data support that KPC2 regulates Hoxa2 by promoting its relocation to the cytoplasm. (C) 2015 Elsevier B.V. All rights reserved.