Meersseman G, Verschueren K, Nelles L, Blumenstock C, Kraft H, Wuytens G, Remacle J, Kozak C A, Tylzanowski P, Niehrs C, Huylebroeck D
Department of Cell Growth, Differentiation and Development, Flanders Interuniversity Institute for Biotechnology (VIB), Leuven, Belgium.
Mech Dev. 1997 Jan;61(1-2):127-40. doi: 10.1016/s0925-4773(96)00629-6.
We report the characterization of two vertebrate homologs of Drosophila mothers against dpp (Mad) isolated from the mouse and the Xenopus embryo, named MusMLP (mad-like protein) and XenMLP, respectively, together with a summary of their expression patterns in the embryo. Overexpression of XenMLP causes ventralization of Xenopus embryos and we demonstrate that the C-terminal domain is necessary and sufficient to confer this biological effect. This domain also has the potential for transcriptional activation, as shown in one-hybrid assays in mammalian cells. We further demonstrate that MLPs are multidomain proteins by showing a cis-negative effect of the N-terminal domain on the transactivation by the C-terminal domain and that the proline-rich, middle domain maximizes the activity of the C-terminal domain. We also mapped the MusMLP gene to a region on mouse chromosome 13 that corresponds to a region on human chromosome 5q that contains cancer-related genes.
我们报告了从小鼠和非洲爪蟾胚胎中分离出的果蝇抗dpp（Mad）的两种脊椎动物同源物的特征，分别命名为MusMLP（类Mad蛋白）和XenMLP，并总结了它们在胚胎中的表达模式。XenMLP的过表达导致非洲爪蟾胚胎腹侧化，并且我们证明C末端结构域对于赋予这种生物学效应是必要且充分的。如在哺乳动物细胞的单杂交试验中所示，该结构域也具有转录激活的潜力。我们通过显示N末端结构域对C末端结构域的反式激活的顺式负效应，进一步证明MLP是多结构域蛋白，并且富含脯氨酸的中间结构域可使C末端结构域的活性最大化。我们还将MusMLP基因定位到小鼠13号染色体上的一个区域，该区域对应于人类5号染色体q臂上包含癌症相关基因的区域。
