The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity
The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity
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DOI：
10.1093/emboj/17.5.1434
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发表时间：
1998-03-02
期刊：
影响因子：
11.4
通讯作者：
Blasi, F
中科院分区：
文献类型：
--
作者：
Berthelsen, J;Zappavigna, V;Blasi, F
哺乳动物Pbx和果蝇exd基因的产物能够与Box蛋白特异性相互作用，并增加其DNA结合亲和力和选择性。在随附的论文中，我们表明Pbx蛋白与一种新的同源结构域蛋白Prep 1作为稳定的异源二聚体存在。在这里，我们表明，Prep 1-Pbx相互作用提出了新的结构特征：它是独立的DNA结合和各自的同源结构域的完整性，并需要在N-末端部分的两种蛋白质的序列。Prep 1-Pbx蛋白质-蛋白质相互作用对于DNA结合活性是必不可少的。Prep 1-Pbx复合物存在于早期小鼠胚胎中，此时Pbx也与Box蛋白相互作用。使用不同的相互作用表面可以允许Pbx同时与Prep 1和Hox蛋白相互作用。事实上，我们观察到三元Prep 1-Pbx 1-HOXB 1复合物在体外HOXB 1响应性靶点上的形成。与Prep 1的相互作用增强了HOXB 1-Pbx 1复合物以合作方式从相同靶点激活转录的能力。我们的数据表明，Prep 1是Hox蛋白转录调控中的额外组分。
The products of the mammalian Pbx and Drosophila exd genes are able to interact with Box proteins specifically and to increase their DNA binding affinity and selectivity. Int the accompanying paper we show that Pbx proteins exist as stable heterodimers with a novel homeodomain protein, Prep1. Here we show that Prep1-Pbx interaction presents novel structural features: it is independent of DNA binding and of the integrity of their respective homeodomains, and requires sequences in the N-terminal portions of both proteins. The Prep1-Pbx protein-protein interaction is essential for DNA-binding activity. Prep1-Pbx complexes are present in early mouse embryos at a time when Pbx is also interacting with Box proteins. The use of different interaction surfaces could allow Pbx to interact with Prep1 and Hox proteins simultaneously. Indeed, we observe the formation of a ternary Prep1-Pbx1-HOXB1 complex on a HOXB1-responsive target in vitro. Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target, Our data suggest that Prep1 is an additional component in the transcriptional regulation by Hox proteins.