Role of nuclear expression of YB-1 in cell proliferation

Y-box结合蛋白YB-1是一个在转录和翻译水平上调节基因表达的多功能蛋白家族。肿瘤抑制基因p53通过转录调节基因表达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。凝胶迁移率变动分析表明，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。相反，这种相互作用抑制YB-1的结合。这些发现描绘了通过p53-YB-1相互作用的基因表达的直接机制。我们以前已经表明，Y盒结合蛋白-1（YB-1）优先结合顺铂修饰的Y盒序列。我们发现，蛋白质的冷休克结构域是必要的，但不足以双链DNA结合，而C-尾结构域与单链DNA和RNA相互作用独立的冷休克结构域。在体外翻译系统中，蛋白质翻译抑制YB-1的C-尾结构域可以形成同源二聚体。我们还表征了该蛋白质的内在3 '->5' DNA外切核酸酶活性。我们的研究结果表明，YB-1的功能，在调节DNA/RNA的交易。

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.