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Casein kinase 2 regulates the mRNA-destabilizing activity of tristetraprolin
Authors:Lee Won Hyeok  Lee Hyun Hee  Vo Mai-Tram  Kim Hyo Jeong  Ko Myoung Seok  Im Yeong-Cheol  Min Young Joo  Lee Byung Ju  Cho Wha Ja  Park Jeong Woo
Institution:Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
Abstract:Tristetraprolin (TTP) is an AU-rich element-binding protein that regulates mRNA stability. We previously showed that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells. The p38 MAPK pathway is known to suppress the TTP activity. However, until now the signaling pathway to enhance TTP function is not well known. Here, we show that casein kinase 2 (CK2) enhances the TTP function in the regulation of the VEGF expression in colon cancer cells. CK2 increased TTP protein levels and enhanced VEGF mRNA decaying activity of TTP. TTP was not a direct target of CK2. Instead, CK2 increased the phosphorylation of MKP-1, which led to a decrease in the phosphorylation of p38 MAPK. Inhibition of MKP-1 by siRNA attenuated the increase in TTP function and the decrease of p38 phosphorylation induced by CK2α overexpression. TGF-β1 increased the expressions of CK2 and TTP and the TTP function. The siRNA against CK2α or TTP reversed TGF-β1-induced increases in the expression of CK2 and TTP and the TTP function. Our data suggest that CK2 enhances the protein level and activity of TTP via the modulation of the MKP-1-p38 MAPK signaling pathway and that TGF-β1 enhances the activity of CK2.
Keywords:Colon Cancer  Gene Regulation  Protein Stability  RNA-binding Protein  RNA Turnover  CK2  MKP-1  TGF-beta  VEGF  Tristetraprolin
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