Niessing D, Dostatni N, Jäckle H, Rivera-Pomar R
Max-Planck-Institut für biophysikalische Chemie, Abt. Molekulare Entwicklungsbiologie, Am Fassberg, D-37077 Göttingen, Germany.
EMBO J. 1999 Apr 1;18(7):1966-73. doi: 10.1093/emboj/18.7.1966.
The Drosophila body organizer Bicoid (Bcd) is a maternal homeodomain protein. It forms a concentration gradient along the longitudinal axis of the preblastoderm embryo and activates early zygotic segmentation genes in a threshold-dependent fashion. In addition, Bcd acts as a translational repressor of maternal caudal (cad) mRNA in the anterior region of the embryo. This process involves a distinct Bcd-binding region (BBR) in the 3' untranslated region (UTR) of cad mRNA. Using cotransfection assays, we found that Bcd represses translation in a cap-dependent manner. Bcd-dependent translational repression involves a portion of the PEST motif of Bcd, a conserved protein motif best known for its function in protein degradation. Rescue experiments with Bcd-deficient embryos expressing transgene-derived Bcd mutants indicate that amino acid replacements within the C-terminal portion of the PEST motif prevent translational repression of cad mRNA but allow for Bcd-dependent transcriptional activation. Thus, Bcd contains separable protein domains for transcriptional and translational regulation of target genes. Maternally-derived cad protein in the anterior region of embryos interferes with head morphogenesis, showing that cad mRNA suppression by Bcd is an important control event during early Drosophila embryogenesis.
果蝇体轴组织者双胸蛋白（Bicoid，Bcd）是一种母体同源结构域蛋白。它沿着胚盘前期胚胎的纵轴形成浓度梯度，并以阈值依赖的方式激活早期合子体节基因。此外，Bcd在胚胎前部作为母体尾蛋白（caudal，cad）mRNA的翻译抑制因子发挥作用。这一过程涉及cad mRNA 3'非翻译区（UTR）中一个独特的Bcd结合区域（BBR）。通过共转染实验，我们发现Bcd以帽依赖的方式抑制翻译。Bcd依赖的翻译抑制涉及Bcd的PEST基序的一部分，PEST基序是一种保守的蛋白质基序，因其在蛋白质降解中的功能而最为人所知。用表达转基因衍生的Bcd突变体的Bcd缺陷胚胎进行的拯救实验表明，PEST基序C端部分的氨基酸替换可阻止cad mRNA的翻译抑制，但允许Bcd依赖的转录激活。因此，Bcd含有用于靶基因转录和翻译调控的可分离蛋白结构域。胚胎前部母体来源的cad蛋白会干扰头部形态发生，这表明Bcd对cad mRNA的抑制是果蝇早期胚胎发育过程中的一个重要调控事件。
