Regulation of Macrophage Ceruloplasmin Gene Expression: One Paradigm of 3'-UTR-mediated Translational Control

Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-γ in U937 monocytic cells, but synthesis of Cp protein is halted after about 12 h by transcript-specific translational silencing. The silencing m...

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Bibliographic Details
Published in:Molecules and cells 2005-10, Vol.20 (2), p.167-172
Main Authors: Mazumder, Barsanjit (Cleveland State University, Cleveland, OH, USA), Sampath, Prabha (University of Washington, Seattle, WA, USA), Fox, Paul L. (Cleveland State University, Cleveland, OH, USA), E-mail: foxp@ccf.org
Format: Article
Language:English
Subjects:
3' Untranslated Regions - physiology
3'-untranslated Region
Animals
Base Sequence
Ceruloplasmin - biosynthesis
Ceruloplasmin - genetics
FERROXIDASA
FERROXIDASE
FERROXYDASE
GAIT Complex
Gene Expression Regulation - physiology
Humans
INFLAMACION
INFLAMMATION
Iron Metabolism
MACROFAGOS
MACROPHAGE
MACROPHAGES
Macrophages - metabolism
Macrophages - physiology
Molecular Sequence Data
Protein Biosynthesis - physiology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Translational Control
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Summary:Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-γ 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.
ISSN:1016-8478
DOI:10.1016/S1016-8478(23)13213-4