YB-1 is important for an early stage embryonic development - Neural tube formation and cell proliferation

YB-1 is important for an early stage embryonic development - Neural tube formation and cell proliferation
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DOI:
10.1074/jbc.m605948200
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发表时间:
2006-12-29
影响因子:
4.8
通讯作者:
Kohno, Kimitoshi
Kohno, Kimitoshi
中科院分区:
生物学2区
文献类型:
--
作者:
Uchiumi, Takeshi;Fotovati, Abbas;Kohno, Kimitoshi

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真核生物Y-box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敲除小鼠,这些小鼠是胚胎致死的,并表现出与神经上皮内细胞增殖异常模式相关的畸形。在YB-1零胚和YB-1(-/-)小鼠胚胎成纤维细胞中β - Actin表达和F-actin形成减少,提示神经管缺损是由神经上皮内细胞形态和肌动蛋白组装异常引起的。来自YB-1(-/-)胚胎的成纤维细胞显示出生长和细胞密度降低。集落形成实验表明,YB-1(-/-)小鼠胚胎成纤维细胞在培养中未能发生形态转化,并保持接触抑制。这些结果表明,YB-1参与了小鼠早期发育,包括神经管闭合和细胞增殖。
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.