title: Casein kinase 2 regulates the mRNA-destabilizing activity of tristetraprolin.
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.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Won Hyeok
authors.initials: WH
authors.lastname: Lee
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Mai-Tram
authors.initials: MT
authors.lastname: Vo
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Myoung Seok
authors.initials: MS
authors.lastname: Ko
authors.forename: Yeong-Cheol
authors.initials: YC
authors.lastname: Im
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D047390:Casein Kinase II / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D010766:Phosphorylation; D020871:RNA Stability / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D051816:Tristetraprolin / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D051816:Tristetraprolin; D042461:Vascular Endothelial Growth Factor A; D047390:Casein Kinase II; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1