Uchiumi Takeshi, Fotovati Abbas, Sasaguri Takakazu, Shibahara Kohtaro, Shimada Tatsuo, Fukuda Takao, Nakamura Takanori, Izumi Hiroto, Tsuzuki Teruhisa, Kuwano Michihiko, Kohno Kimitoshi
Department of Molecular Biology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
J Biol Chem. 2006 Dec 29;281(52):40440-9. doi: 10.1074/jbc.M605948200. Epub 2006 Nov 2.
The eukaryotic Y-box-binding protein-1 (YB-1) is involved in the transcriptional and translational control of many biological processes, including cell proliferation. In clinical studies, the cellular level of YB-1 closely correlates with tumor growth and prognosis. To understand the role of YB-1 in vivo, especially in the developmental process, we generated YB-1 knock-out mice, which are embryonic lethal and exhibit exencephaly associated with abnormal patterns of cell proliferation within the neuroepithelium. beta-Actin expression and F-actin formation were reduced in the YB-1 null embryo and YB-1(-/-) mouse embryonic fibroblasts, suggesting that the neural tube defect is caused by abnormal cell morphology and actin assembly within the neuroepithelium. Fibroblasts derived from YB-1(-/-) embryos demonstrated reduced growth and cell density. A colony formation assay showed that YB-1(-/-) mouse embryonic fibroblasts failed to undergo morphological transformation and remained contact-inhibited in culture. These results demonstrate that YB-1 is involved in early mouse development, including neural tube closure and cell proliferation.
真核生物Y盒结合蛋白1（YB-1）参与许多生物过程的转录和翻译控制，包括细胞增殖。在临床研究中，YB-1的细胞水平与肿瘤生长和预后密切相关。为了了解YB-1在体内的作用，特别是在发育过程中的作用，我们构建了YB-1基因敲除小鼠，这些小鼠胚胎致死，并表现出与神经上皮内细胞增殖异常模式相关的无脑畸形。在YB-1基因敲除胚胎和YB-1（-/-）小鼠胚胎成纤维细胞中，β-肌动蛋白表达和F-肌动蛋白形成减少，这表明神经管缺陷是由神经上皮内异常的细胞形态和肌动蛋白组装引起的。来自YB-1（-/-）胚胎的成纤维细胞生长和细胞密度降低。集落形成试验表明，YB-1（-/-）小鼠胚胎成纤维细胞在培养中未能发生形态转化，仍保持接触抑制。这些结果表明，YB-1参与小鼠早期发育，包括神经管闭合和细胞增殖。
