The RNA-binding protein HuR stabilizes cytosolic phospholipase A 2α mRNA under Interleukin-1β treatment in non-small cell lung cancer A549 cells

Wan Lin Liao, Wei Chiao Wang, Wen Chang Chang, Joseph T. Tseng

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23 引文 斯高帕斯(Scopus)

摘要

The activation of cytosolic phospholipase A 2α (cPLA 2α) plays an important role in initiating the inflammatory response. The regulation of cPLA 2α mRNA turnover has been proposed to control cPLA 2α gene expression under cytokine and growth factor stimulation. However, the detailed mechanism is still unknown. In this report, we have demonstrated that the cPLA 2α mRNA stability was increased under IL-1β treatment in A549 cells. By using EMSAs, HuR was identified as binding with the cPLA 2α mRNA 3′-UTR, and the binding region was located at nucleotides 2716-2807, a fragment containing AUUUA flanked by U-rich sequences. IL-1β treatment enhanced the association of cPLA 2α mRNA with cytosolic HuR. The reduction of HuR expression by RNA interference technology inhibited IL-1β-induced cPLA 2α mRNA and protein expression. Furthermore, blocking the p38 MAPK signaling pathway with SB203580 abolished the effect of IL-1β-induced cPLA 2α gene expression. Phosphorylation at residue Thr-118 of HuR is crucial in regulating the interaction between HuR and its target mRNAs. Mutation of HuR Thr-118 reduced the association between HuR and cPLA 2α mRNA under IL-1β treatment. This inhibitory effect was also observed in binding with COX-2 mRNA. This result indicated that p38 MAPK-mediated Thr-118 phosphorylation may play a key role in regulating the interaction of HuR with its target mRNAs in inflammation.

原文英語
頁(從 - 到)35499-35508
頁數10
期刊Journal of Biological Chemistry
286
發行號41
DOIs
出版狀態已發佈 - 十月 14 2011

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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