热激蛋白Hsp72促进热休克下HuR对p21CIP1的调控作用

RNA结合蛋白HuR可以结合并调控靶标mRNA稳定性与翻译，但影响HuR 结合活性的因素有待探讨。本研究从蛋白质-蛋白质相互作用角度对影响HuR 与RNA结合活性的因素做了探讨。结果发现，热激蛋白Hsp72在细胞浆与HuR相互作用并促进HuR与p21 (KIP1) 3′UTR（3′非翻译区）的结合； 热休克下Hsp72总蛋白质及细胞浆蛋白质水平上调、但HuR总蛋白质及细胞浆蛋白质水平不变|热休克下HuR与p21 3′UTR的相互作用加强、p21蛋白及mRNA水平上调。上述结果提示，Hsp72可通过与HuR相互作用促进后者与p21 mRNA的结合，进而加强热休克下HuR对p21的表达的促进作用。这些结果为进一步解析HuR的生物学作用机制提供了实验依据。

Hsp72 Enhances the Effect of HuR to Regulate p21CIP1 Expression

RNA binding protein HuR regulates mRNA stability and translation through binding to target mRNAs. However, factors influencing the RNA binding affinity of HuR remain to be studied. In this study, we investigated whether the RNA binding affinity of HuR could be influenced by protein-protein interaction. We found that Hsp72 interacted with HuR in the cytoplasm. Interaction of Hsp72 with HuR enhanced the binding of HuR to the 3′UTR (3′untranslated region) of p21 (KIP1). HeLa cells exposed to heat shock exhibited elevated total and cytoplasmic protein levels of Hsp72, while the total and cytoplasmic protein levels of HuR kept unchanged. The interaction of HuR with p21 3′UTR and the expression of p21 increased with heat shock. In sum, Hsp72 enhances the binding of HuR to p21 mRNA by interacting with HuR. The Hsp72-HuR-p21 regulatory process impacts on the upregulation of p21 by HuR in heat shock. Our findings provide evidence for elucidating the mechanisms controlling the RNA binding affinity of HuR.