Han Zhe, Li Xiumin, Wu Jiang, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12567-72. doi: 10.1073/pnas.0405085101. Epub 2004 Aug 16.
Serum response factor (SRF) regulates genes involved in cell proliferation, migration, cytoskeletal organization, and myogenesis. Myocardin and myocardin-related transcription factors (MRTFs) act as powerful transcriptional coactivators of SRF in mammalian cells. We describe an MRTF from Drosophila, called DMRTF, which shares high homology with the functional domains of mammalian myocardin and MRTFs. DMRTF forms a ternary complex with and stimulates the activity of Drosophila SRF, which has been implicated in branching of the tracheal (respiratory) system and formation of wing interveins. A loss-of-function mutation introduced into the DMRTF locus by homologous recombination results in abnormalities in tracheal branching similar to those in embryos lacking SRF. Misexpression in wing imaginal discs of a dominant negative DMRTF mutant also causes a diminution of wing interveins, whereas overexpression of DMRTF results in excess intervein tissue, abnormalities reminiscent of SRF loss- and gain-of-function phenotypes, respectively. Overexpression of these DMRTF mutants in mesoderm and in the tracheal system also perturbs mesoderm cell migration and tracheal branching, respectively. We conclude that the interaction of MRTFs with SRF represents an ancient protein partnership involved in cytoplasmic outgrowth and cell migration during development.
血清反应因子（SRF）调控参与细胞增殖、迁移、细胞骨架组织和肌生成的基因。心肌蛋白和心肌蛋白相关转录因子（MRTFs）在哺乳动物细胞中作为SRF强大的转录共激活因子发挥作用。我们描述了一种来自果蝇的MRTF，称为DMRTF，它与哺乳动物心肌蛋白和MRTFs的功能域具有高度同源性。DMRTF与果蝇SRF形成三元复合物并刺激其活性，果蝇SRF与气管（呼吸）系统的分支和翅脉的形成有关。通过同源重组引入DMRTF基因座的功能缺失突变导致气管分支异常，类似于缺乏SRF的胚胎中的异常。显性负性DMRTF突变体在翅成虫盘的错误表达也会导致翅脉减少，而DMRTF的过表达则会导致翅脉组织过多，这些异常分别让人联想到SRF功能缺失和功能获得的表型。这些DMRTF突变体在中胚层和气管系统中的过表达也分别扰乱了中胚层细胞迁移和气管分支。我们得出结论，MRTFs与SRF的相互作用代表了一种古老的蛋白质伙伴关系，参与发育过程中的细胞质生长和细胞迁移。
