Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo

Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo
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DOI:
10.7554/elife.06034
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发表时间:
2015-04-14
期刊:
影响因子:
7.7
通讯作者:
Merabet, Samir
Merabet, Samir
中科院分区:
生物学1区
文献类型:
--
作者:
Baeza, Manon;Viala, Severine;Merabet, Samir

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Hox蛋白是成熟的发育调节因子,其在整个胚胎发生中协调细胞命运和形态发生。相比之下,我们对其特定分子作用模式的了解仅限于与少数辅因子的相互作用。在这里,我们表明,Hox蛋白能够与广泛的转录因子在活的果蝇胚胎相互作用。在这种情况下,特异性依赖于保守的短线性基序(SLiM)的通用用途,令人惊讶的是,这往往会抑制Hox蛋白的相互作用潜力。在不同组织中观察到SLiMs的这种新型缓冲活性,并在从刺胞动物到小鼠物种的Hox蛋白中发现。虽然这些相互作用仍有待分析的背景下,内源性的Hox调控活动,我们的观察挑战传统的角色分配给SLiMs和提供一个替代的概念来解释如何Hox相互作用组特异性可以实现在胚胎发育过程中。
Hox proteins are well-established developmental regulators that coordinate cell fate and morphogenesis throughout embryogenesis. In contrast, our knowledge of their specific molecular modes of action is limited to the interaction with few cofactors. Here, we show that Hox proteins are able to interact with a wide range of transcription factors in the live Drosophila embryo. In this context, specificity relies on a versatile usage of conserved short linear motifs (SLiMs), which, surprisingly, often restrains the interaction potential of Hox proteins. This novel buffering activity of SLiMs was observed in different tissues and found in Hox proteins from cnidarian to mouse species. Although these interactions remain to be analysed in the context of endogenous Hox regulatory activities, our observations challenge the traditional role assigned to SLiMs and provide an alternative concept to explain how Hox interactome specificity could be achieved during the embryonic development.