Role of nuclear expression of YB-1 in cell proliferation

Y-box结合蛋白YB-1属于多功能蛋白家族，在转录和翻译水平上调节基因表达。肿瘤抑制基因P53通过转录调控来调节基因表达，从而显示出抑制生长的特性。我们现在证明YB-1与P53直接相互作用。凝胶迁移率改变分析表明，YB-1与P53的相互作用刺激了P53与其共同序列的序列特异性DNA结合。相反，这种相互作用抑制了YB-1的结合。这些发现描绘了一个通过P53-YB-1相互作用来表达基因的直接机制。我们以前已经证明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，但不是充分的，而C-尾部结构域独立于冷休克结构域与单链DNA和RNA相互作用。在体外翻译系统中，该蛋白的C-尾区抑制了YB-1的翻译，可以形成同源二聚体。我们还鉴定了该蛋白的内在3‘--&gt；5’DNA外切酶活性。我们的研究结果表明，YB-1在调节DNA/RNA交易中发挥作用。

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.