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pubmed:abstractText |
Ferritin, which is composed of H and L subunits, plays an important role in iron storage and in the control of intracellular iron distribution. Synthesis of both ferritin subunits is controlled by a common cytosolic protein, iron regulatory protein (IRP), which binds to the iron-responsive element (IRE) in the 5'-UTR of the H- and L-ferritin mRNAs. In the present study, we have identified a single point mutation (A49U) in the IRE motif of H-ferritin mRNA, in four of seven members of a Japanese family affected by dominantly inherited iron overload. Gel-shift mobility assay and Scatchard-plot analysis revealed that a mutated IRE probe had a higher binding affinity to IRP than did the wild-type probe. When mutated H subunit was overexpressed in COS-1 cells, suppression of H-subunit synthesis and of the increment of radiolabeled iron uptake were observed. These data suggest that the A49U mutation in the IRE of H-subunit is responsible for tissue iron deposition and is a novel cause of hereditary iron overload, most likely related to impairment of the ferroxidase activity generated by H subunit.
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pubmed:affiliation |
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
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