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Role of nuclear expression of YB-1 in cell proliferation

YB-1核表达在细胞增殖中的作用

基本信息

批准号：
11670152
负责人：
KOHNO Kimitoshi
金额：
$ 2.24万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670152/
关键词：
YB-1 cisplatin p53 MDR1 p21 exonuclease 卵巣癌大腸癌細胞増殖 Topo II PCNA

项目摘要

The Y-box binding protein, YB-1, belongs to a family of multifunctional proteins which regulate gene expression on both transcriptional and translational levels. The tumor suppressor gene p53 displays growth suppressive properties by regulating gene expression through transcriptional regulation. We now demonstrate that YB-1 directly interacts with p53. Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-specific DNA binding of p53 to its consensus sequence. By contrast, this interaction inhibited the binding of YB-1. These findings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction. We have previously shown that Y box-binding protein-1 (YB-1) binds preferentially to cisplatin-modified Y box sequences. We found that the cold shock domain of the protein is necessary but not sufficient for double-stranded DNA binding while the C-tail domain interacts with both single-stranded DNA and RNA independently of the cold shock domain. In an in vitro translation system the C-tail domain of the protein inhibited translation YB-1 can form a homodimer. We also characterized an intrinsic 3'-->5' DNA exonuclease activity of the protein. Our findings suggest that YB-1 functions in regulating DNA/RNA transactions.

Y-box 结合蛋白 YB-1 属于多功能蛋白家族，可在转录和翻译水平上调节基因表达。肿瘤抑制基因 p53 通过转录调节来调节基因表达，从而显示出生长抑制特性。我们现在证明 YB-1 直接与 p53 相互作用。凝胶迁移率变化分析表明，YB-1 与 p53 的相互作用刺激了 p53 与其共有序列的序列特异性 DNA 结合。相比之下，这种相互作用抑制了 YB-1 的结合。这些发现描绘了通过 p53-YB-1 相互作用进行基因表达的简单机制。我们之前已经证明，Y 盒结合蛋白-1 (YB-1) 优先与顺铂修饰的 Y 盒序列结合。我们发现蛋白质的冷休克结构域对于双链 DNA 结合是必要的，但还不够，而 C 尾结构域与单链 DNA 和 RNA 相互作用，独立于冷休克结构域。在体外翻译系统中，抑制翻译的蛋白质 YB-1 的 C 尾结构域可以形成同二聚体。我们还表征了该蛋白质的内在 3'-->5' DNA 核酸外切酶活性。我们的研究结果表明 YB-1 具有调节 DNA/RNA 交易的功能。