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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)
Publication Information
Molecules and Cells / v.20, no.2, 2005 , pp. 167-172 More about this Journal
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
3'-untranslated Region; Ceruloplasmin; GAIT Complex; Inflammation; Iron Metabolism; Macrophage; Translational Control;
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