Human HOX Proteins Use Diverse and Context-Dependent Motifs to Interact with TALE Class Cofactors
Human HOX Proteins Use Diverse and Context-Dependent Motifs to Interact with TALE Class Cofactors
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DOI：
10.1016/j.celrep.2018.02.070
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发表时间：
2018-03-13
期刊：
影响因子：
8.8
通讯作者：
Merabet, Samir
中科院分区：
文献类型：
--
作者：
Dard, Amelie;Reboulet, Jonathan;Merabet, Samir
HOX蛋白通过与TALE类PBX和MEIS辅助因子相互作用实现多种功能。与这种在发育和疾病方面建立的伙伴关系形成对比的是，Hox蛋白如何与PBX和Meis相互作用仍不清楚。在这里，我们提出了一个系统的分析HOX/PBX/MEIS相互作用的性质，在体外和活细胞中扫描所有含有人和小鼠HOX蛋白的平行对数组。我们证明了一个先前描述的对HOX-PBX相互作用至关重要的HOX蛋白基序在除两个最前面的副对数组外的所有MEI的存在中都变得不可或缺。我们进一步确定了以高度依赖于上下文的方式使用的Paralog特定的故事结合位点。其中一个结合位点与HOXA7在乳腺癌细胞中的增殖活性有关。总而言之，这些发现揭示了HOX蛋白和它们的主要发育辅助因子之间非凡水平的相互作用灵活性。
HOX proteins achieve numerous functions by interacting with the TALE class PBX and MEIS cofactors. In contrast to this established partnership in development and disease, how HOX proteins could interact with PBX and MEIS remains unclear. Here, we present a systematic analysis of HOX/PBX/MEIS interaction properties, scanning all paralog groups with human and mouse HOX proteins in vitro and in live cells. We demonstrate that a previously characterized HOX protein motif known to be critical for HOX-PBX interactions becomes dispensable in the presence of MEIS in all except the two most anterior paralog groups. We further identify paralog-specific TALE-binding sites that are used in a highly context-dependent manner. One of these binding sites is involved in the proliferative activity of HOXA7 in breast cancer cells. Together these findings reveal an extraordinary level of interaction flexibility between HOX proteins and their major class of developmental cofactors.