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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies have shown that ferritin within developing avian corneal epithelial cells is predominantly a nuclear protein and that one function of the molecule in this location is to protect DNA from UV damage. To elucidate the mechanism for this tissue-specific nuclear translocation, cultured corneal epithelial cells and corneal fibroblasts were transfected with a series of deletion constructs for the heavy chain of ferritin, ferritin-H, tagged with a human c-myc epitope. The subcellular localization of the ferritin was determined by immunofluorescence for the myc-tag. For the corneal epithelial cells, the first 10 or the last 30 amino acids of ferritin-H could be deleted without affecting the nuclear localization. However, larger deletions of these areas, or deletions along the length of the body of the molecule, resulted largely in retention of the truncated proteins within the cytoplasm. Thus, it seems that no specific region functions as an NLS. Immunoblotting analysis of SDS-PAGE-separated extracts suggests that assembly of the supramolecular form of ferritin is not necessary for successful nuclear translocation, because one deletion construct that failed to undergo supramolecular assembly showed nuclear localization. In transfected fibroblasts, the endogenous ferritin remained predominantly in the cytoplasm, as did that synthesized from transfected full-length ferritin constructs and from two deletion constructs encoding truncated chains that could still assemble into the supramolecular form of ferritin. However, those truncated chains that were unable to participate in supramolecular assembly generally showed both nuclear and cytoplasmic localization, indicating that, in this cell type, supramolecular assembly is involved in restricting ferritin to the cytoplasm. These data suggest that for corneal epithelial cells, the nuclear localization of ferritin most likely involves a tissue-specific mechanism that facilitates transport into the nucleus, whereas, in fibroblasts, the cytoplasmic retention involves supramolecular assembly that prevents passive diffusion into the nucleus.
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PMID:Nuclear translocation of ferritin in corneal epithelial cells. 1149 71

Ferritin is traditionally considered a cytoplasmic iron-storage protein, but recent reports indicate that it is also found in cell nuclei. Nuclear ferritin has been proposed to be involved in both the protection of DNA and the exacerbation of iron-induced oxidative damage to DNA. We demonstrate that H-rich ferritin is present in the nucleus of human astrocytoma tumor cells. To study the mechanism and regulation of ferritin translocation to the nucleus, we developed a cell culture model using SW1088 human astrocytoma cells. Changes in cellular iron levels, cytokine treatments and hydrogen peroxide exposure affected the distribution of ferritin between the cytosol and the nucleus. Ferritin enters the nucleus via active transport through the nuclear pore and does not require NLS-bearing cytosolic factors for transport. Furthermore, H-rich ferritin is preferred over L-rich ferritin for uptake into the nucleus. Whole cell crosslinking studies revealed that ferritin is associated with DNA. Ferritin protected DNA from iron-induced oxidative damage in both in vitro and in cell culture models. These results strongly suggest a novel role for ferritin in nuclear protection. This work should lead to novel characterization of ferritin functions in the context of genomic stability and may have unparalleled biological significance in terms of the accessibility of metals to DNA. The knowledge generated as a result of these studies will also improve our understanding of iron-induced damage of nuclear constituents.
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PMID:Regulation, mechanisms and proposed function of ferritin translocation to cell nuclei. 1197 57