热激蛋白Hsp72促进热休克下HuR对p21^(CIP1)的调控作用

Hsp72 Enhances the Effect of Hu R to Regulate p21^(CIP1) Expression

RNA结合蛋白Hu R可以结合并调控靶标m RNA稳定性与翻译,但影响Hu R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Hu R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Hu R相互作用并促进Hu R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Hu R总蛋白质及细胞浆蛋白质水平不变;热休克下Hu R与p21 3'UTR的相互作用加强、p21蛋白及m RNA水平上调。上述结果提示,Hsp72可通过与Hu R相互作用促进后者与p21 m RNA的结合,进而加强热休克下Hu R对p21的表达的促进作用。这些结果为进一步解析Hu R的生物学作用机制提供了实验依据。

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