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PMID: 21507959 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Casein kinase 2 regulates the mRNA-destabilizing activity of tristetraprolin.

The Journal of biological chemistry ·Vol. 286 ·No. 24 ·2011-06-17 ·Pages 21577-87

Lee WH, Lee HH, Vo MT, Kim HJ, Ko MS, Im YC, Min YJ, Lee BJ, Cho WJ, Park JW

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.

MeSH Terms
Casein Kinase II/metabolism Cell Line, Tumor Colonic Neoplasms/metabolism Dual Specificity Phosphatase 1/metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans MAP Kinase Signaling System Models, Biological Phosphorylation RNA Stability/genetics RNA, Small Interfering/metabolism Transforming Growth Factor beta1/metabolism Tristetraprolin/chemistry Vascular Endothelial Growth Factor A/metabolism
Chemicals
RNA, Small Interfering Transforming Growth Factor beta1 Tristetraprolin Vascular Endothelial Growth Factor A Casein Kinase II DUSP1 protein, human Dual Specificity Phosphatase 1
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Lee Won Hyeok
Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
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
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M110.201137
Published
2011-06-17
Epub
2011-00-20
Pages
21577-87
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3122216
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M110.201137 PMC Full Text View journal details
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