The p53 protein is one of the transcription factors responsible for cell cycle regulation and prevention of cancer development. Its expression is regulated at the transcriptional, translational and post-translational levels. Recent years of research have shown that the 5ʹ terminus of p53 mRNA plays an important role in this regulation. This region seems to be a docking platform for proteins involved in p53 expression, particularly under stress conditions. Here, we applied RNA-centric affinity chromatography to search for proteins that bind to the 5ʹ terminus of p53 mRNA and thus may be able to regulate the p53 expression profile. We found heterogeneous nuclear ribonucleoprotein K, hnRNP K, to be one of the top candidates. Binding of hnRNP K to the 5ʹ-terminal region of p53 mRNA was confirmed in vitro. We demonstrated that changes in the hnRNP K level in the cell strongly affected the p53 expression profile under various stress conditions. Downregulation or overexpression of hnRNP K caused a decrease or an increase in the p53 mRNA amount, respectively, pointing to the transcriptional mode of expression regulation. However, when hnRNP K was overexpressed under endoplasmic reticulum stress and the p53 amount has elevated no changes in the p53 mRNA level were detected suggesting translational regulation of p53 expression. Our findings have shown that hnRNP K is not only a mutual partner of p53 in the transcriptional activation of target genes under stress conditions but it also acts as a regulator of p53 expression at the transcriptional and potentially translational levels.

p53蛋白是负责细胞周期调控和预防癌症发展的转录因子之一。它的表达在转录，翻译和翻译后水平受到调控。近年来的研究表明，p53 mRNA的5′末端在该调节中起重要作用。该区域似乎是参与p53表达的蛋白质的停靠平台，尤其是在压力条件下。在这里，我们应用了以RNA为中心的亲和层析来寻找与p53 mRNA 5'末端结合的蛋白质，因此可能能够调节p53表达谱。我们发现异质核核糖核蛋白K，hnRNP K，是最佳候选人之一。在体外证实hnRNP K与p53 mRNA 5′端区域结合。我们证明了在各种压力条件下，细胞中hnRNP K水平的变化会强烈影响p53表达谱。hnRNP K的下调或过表达分别导致p53 mRNA量的减少或增加，这表明表达调控的转录方式。但是，当hnRNP K在内质网应激下过表达且p53量升高时，未检测到p53 mRNA水平的变化，提示p53表达的翻译调控。我们的发现表明，hnRNP K不仅是应激条件下目标基因转录激活中p53的共同伴侣，而且在转录和潜在翻译水平上还充当p53表达的调节剂。