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Translational control of ceruloplasmin gene expression: Beyond the IRE
Mazumder, Barsanjit; Sampath, Prabha; Fox, Paul L.
  • Mazumder, Barsanjit; Cleveland State University. Department of Biology. Cleveland. US
  • Sampath, Prabha; University of Washington. Department of Pathology. Seattle. US
  • Fox, Paul L; Cleveland Clinic Foundation. Lerner Research Institute. Department of Cell Biology. Cleveland. US
Biol. Res ; 39(1): 59-66, 2006. ilus
Article in English | LILACS | ID: lil-430698
ABSTRACT
Translational control is a common regulatory mechanism for the expression of iron-related proteins. For example, three enzymes involved in erythrocyte development are regulated by three different control mechanisms globin synthesis is modulated by heme-regulated translational inhibitor; erythroid 5-aminolevulinate synthase translation is inhibited by binding of the iron regulatory protein to the iron response element in the 5'-untranslated region (UTR); and 15-lipoxygenase is regulated by specific proteins binding to the 3'-UTR. Ceruloplasmin (Cp) is a multi-functional, copper protein made primarily by the liver and by activated macrophages. Cp has important roles in iron homeostasis and in inflammation. Its role in iron metabolism was originally proposed because of its ferroxidase activity and because of its ability to stimulate iron loading into apo-transferrin and iron efflux from liver. We have shown that Cp mRNA is induced by interferon (IFN)-ã in U937 monocytic cells, but synthesis of Cp protein is halted by translational silencing. The silencing mechanism requires binding of a cytosolic inhibitor complex, IFN-Gamma-Activated Inhibitor of Translation (GAIT), to a specific GAIT element in the Cp 3'-UTR. Here, we describe our studies that define and characterize the GAIT element and elucidate the specific trans-acting proteins that bind the GAIT element. Our experiments describe a new mechanism of translational control of an iron-related protein and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.
Subject(s)
Full text: Available Index: LILACS (Americas) Main subject: Protein Biosynthesis / Ceruloplasmin / Iron-Regulatory Proteins / Iron Limits: Animals / Humans Language: English Journal: Biol. Res Journal subject: Biology Year: 2006 Type: Article / Project document Affiliation country: United States Institution/Affiliation country: Cleveland Clinic Foundation/US / Cleveland State University/US / University of Washington/US

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Full text: Available Index: LILACS (Americas) Main subject: Protein Biosynthesis / Ceruloplasmin / Iron-Regulatory Proteins / Iron Limits: Animals / Humans Language: English Journal: Biol. Res Journal subject: Biology Year: 2006 Type: Article / Project document Affiliation country: United States Institution/Affiliation country: Cleveland Clinic Foundation/US / Cleveland State University/US / University of Washington/US