Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Regulation of Macrophage Ceruloplasmin Gene Expression: One Paradigm of 3'-UTR-mediated Translational Control

  • Mazumder, Barsanjit (Department of Biology, Geology, and Environmental Sciences, Cleveland State University) ;
  • Sampath, Prabha (Department of Pathology, University of Washington) ;
  • Fox, Paul L. (Department of Biology, Geology, and Environmental Sciences, Cleveland State University)
  • Received : 2005.10.12
  • Accepted : 2005.10.14
  • Published : 2005.10.31
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Abstract

Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-${\gamma}$ in U937 monocytic cells, but synthesis of Cp protein is halted after about 12 h by transcript-specific translational silencing. The silencing mechanism requires binding of a 4-component cytosolic inhibitor complex, IFN-gamma-activated inhibitor of translation (GAIT), to a defined structural element (GAIT element) in the Cp 3'-UTR. Translational silencing of Cp mRNA requires the essential proteins of mRNA circularization, suggesting that the translational inhibition requires end-to-end mRNA closure. These studies describe a new mechanism of translational control, and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.

Keywords

Acknowledgement

Supported by : National Institutes of Health

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