Zhao Chen, Fu Dechen, Dave Vrushank, Ma Jun
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
J Biol Chem. 2003 Nov 7;278(45):43901-9. doi: 10.1074/jbc.M302714200. Epub 2003 Aug 25.
Bicoid is a molecular morphogen-controlling embryonic patterning in Drosophila. It is a homeodomain-containing protein that activates specific target genes during early embryogenesis. Our recent studies have identified a domain of Bcd located outside its homeodomain and referred to as a self-inhibitory domain that can dramatically repress its own ability to activate transcription. Here we present evidence that the self-inhibitory function is evolutionarily conserved. A systematic analysis of this domain reveals a composite 10-amino acid motif with interdigitating residues that regulate Bcd activity in opposite manners. Mutations within the Bcd motif can exert their respective effects when the self-inhibitory domain is grafted to an entirely heterologous activator, but they do not affect DNA binding in vitro or subcellular localization of Bcd in cells. We further show that the self-inhibitory domain of Bcd can interact with Sin3A, a component of the histone deacetylase co-repressor complex. Our study suggests that the activity of Bcd is intricately controlled by multiple mechanisms involving the actions of co-repressor proteins.
双尾蛋白是一种控制果蝇胚胎模式形成的分子形态发生素。它是一种含有同源结构域的蛋白质，在胚胎早期发育过程中激活特定的靶基因。我们最近的研究确定了双尾蛋白（Bcd）同源结构域之外的一个区域，称为自我抑制结构域，它可以显著抑制自身激活转录的能力。在这里，我们提供证据表明这种自我抑制功能在进化上是保守的。对该结构域的系统分析揭示了一个由10个氨基酸组成的复合基序，其中相互交错的残基以相反的方式调节Bcd的活性。当自我抑制结构域嫁接到完全异源的激活剂上时，Bcd基序内的突变可以发挥各自的作用，但它们不影响体外DNA结合或细胞中Bcd的亚细胞定位。我们进一步表明，Bcd的自我抑制结构域可以与组蛋白去乙酰化酶共抑制复合物的一个组分Sin3A相互作用。我们的研究表明，Bcd的活性受到多种机制的复杂调控，这些机制涉及共抑制蛋白的作用。
