Casein Kinase 2 Regulates the mRNA-destabilizing Activity of Tristetraprolin

• Published in: The Journal of biological chemistry 2011-06, Vol.286 (24), p.21577-21587
• Main 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
• Format: Article
• Language: English
• Subjects: Casein Kinase II - metabolism; Cell Line, Tumor; CK2; Colon Cancer; Colonic Neoplasms - metabolism; Dual Specificity Phosphatase 1 - metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Regulation; Humans; MAP Kinase Signaling System; MKP-1; Models, Biological; Phosphorylation; Protein Stability; RNA Stability - genetics; RNA Turnover; RNA, Small Interfering - metabolism; RNA-binding Protein; TGF-beta; Transforming Growth Factor beta1 - metabolism; Tristetraprolin; Tristetraprolin - chemistry; Vascular Endothelial Growth Factor A - metabolism; VEGF
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.201137

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.