The expression and the molecular network of CSD protein in proliferating disease

Y-box蛋白家族的特征在于具有高度保守的冷休克结构域，其结合核酸并与原核冷休克蛋白共享同源性。真核生物Y盒结合蛋白-1（YB-1）参与包括细胞增殖在内的许多生物学过程的转录和翻译调控。在临床研究中，YB-1的细胞水平与肿瘤的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，我们产生了YB-1基因敲除小鼠，这是胚胎致死，并表现出露脑与神经上皮细胞增殖的异常模式。β-肌动蛋白表达和F-肌动蛋白形成在YB-1缺失胚胎和YB-1敲除小鼠胚胎成纤维细胞中减少，表明神经管缺陷是由神经上皮内的异常细胞形态和肌动蛋白组装引起的。来自YB-1/胚胎的成纤维细胞表现出降低的生长和细胞密度。集落形成试验表明YB-1/小鼠胚胎成纤维细胞不能发生形态学转化，在培养中保持接触抑制。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。

The Y-box protein family is characterized by a highly conserved cold-shock domain that binds nucleic acids and shares homology with the prokaryotic cold-shock proteins. 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 knockout 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.