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Casein kinase 2 regulates the mRNA-destabilizing activity of tristetraprolin

Won Hyeok Lee1, Hyun Hee Lee, Mai-Tram Vo

  • 1Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.

The Journal of Biological Chemistry
|April 22, 2011
PubMed

Insights

Casein kinase 2 (CK2) enhances tristetraprolin (TTP) function in colon cancer by modulating the MKP-1-p38 MAPK pathway, increasing TTP levels and VEGF mRNA decay. TGF-β1 also boosts CK2 and TTP activity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Signal Transduction

Background:

  • Tristetraprolin (TTP) is an AU-rich element-binding protein regulating mRNA stability and acts as a negative regulator of VEGF gene expression in colon cancer.
  • The p38 MAPK pathway is known to suppress TTP activity, but pathways enhancing TTP function remain largely unknown.

Purpose of the Study:

  • To investigate the signaling pathway that enhances TTP function in regulating VEGF expression in colon cancer cells.
  • To elucidate the role of casein kinase 2 (CK2) in modulating TTP activity and its downstream effects.

Main Methods:

  • Investigated the effect of CK2 on TTP protein levels and VEGF mRNA decay activity.
  • Utilized siRNA to inhibit MKP-1 and assessed its impact on TTP function and p38 MAPK phosphorylation.
  • Examined the influence of TGF-β1 on CK2 and TTP expression and function, and the effect of siRNA against CK2α or TTP.

Main Results:

  • CK2 was found to enhance TTP function by increasing TTP protein levels and augmenting TTP's VEGF mRNA decaying activity.
  • CK2 enhanced TTP function indirectly by increasing MKP-1 phosphorylation, which decreased p38 MAPK phosphorylation.
  • siRNA-mediated inhibition of MKP-1 attenuated CK2-induced increases in TTP function and p38 phosphorylation.
  • TGF-β1 increased CK2 and TTP expression and TTP function; siRNA against CK2α or TTP reversed these effects.

Conclusions:

  • CK2 enhances TTP protein levels and activity through modulation of the MKP-1-p38 MAPK signaling pathway.
  • TGF-β1 enhances CK2 activity, which in turn enhances TTP function in colon cancer cells.

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