Ferritoid, a Tissue-specific Nuclear Transport Protein for Ferritin in Corneal Epithelial Cells
Open accessAbstract
Previously we reported that ferritin in corneal epithelial (CE) cells is a nuclear protein that protects DNA from UV damage. Since ferritin is normally cytoplasmic, in CE cells, a mechanism must exist that effects its nuclear localization. We have now determined that this involves a nuclear transport molecule we have termed ferritoid. Ferritoid is specific for CE cells and is developmentally regulated. Structurally, ferritoid contains multiple domains, including a functional SV40-type nuclear localization signal and a ferritin-like region of approximately 50% similarity to ferritin itself. This latter domain is likely responsible for the interaction between ferritoid and ferritin detected by co-immunoprecipitation analysis. To test functionally whether ferritoid is capable of transporting ferritin into the nucleus, we performed cotransfections of COS-1 cells with constructs for ferritoid and ferritin. Consistent with the proposed nuclear transport function for ferritoid, co-transfections with full-length constructs for ferritoid and ferritin resulted in a preferential nuclear localization of both molecules; this was not observed when the nuclear localization signal of ferritoid was deleted. Moreover, since ferritoid is structurally similar to ferritin, it may be an example of a nuclear transporter that evolved from the molecule it transports (ferritin).
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Mitochondrial ferritin is highly conserved among a wide variety of living creatures, including Drosophila and plants.
“Mitochondrial ferritin is highly conserved among a wide variety of living creatures, including Drosophila (204, 332) and plants (204, 332)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [204]
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Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
Current protocols in molecular biology
(1988) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(88)90131-4 · Cited by 4,234 · see citing works
The ferritins: molecular properties, iron storage function and cellular regulation
Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667 · see citing works
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
Evan, G. I., Lewis, G. K., Ramsay, G. M., & Bishop, J. M. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.12.3610 · Cited by 2,412 · see citing works
Nuclear targeting sequences — a consensus?
Dingwall, C., & Laskey, R. A. (1991) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(91)90184-w · Cited by 1,891 · see citing works
A knowledge base for predicting protein localization sites in eukaryotic cells
Nakai, K., & Kanehisa, M. I. (1992) · Genomics · doi:10.1016/s0888-7543(05)80111-9 · Cited by 1,512 · see citing works
FERRITIN: STRUCTURE, GENE REGULATION, AND CELLULAR FUNCTION IN ANIMALS, PLANTS, AND MICROORGANISMS
Theil, E. C. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.001445 · Cited by 1,337 · see citing works
[31] PHD: Predicting one-dimensional protein structure by profile-based neural networks
Rost, B. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)66033-9 · Cited by 1,282 · see citing works
Ferritin: a cytoprotective antioxidant strategem of endothelium.
Balla, G., Jacob, H., Balla, J., Rosenberg, M. E., Nath, K. A., Apple, F., Eaton, J. W., & Vercellotti, G. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37165-0 · Cited by 1,097 · see citing works
A Novel Receptor-Mediated Nuclear Protein Import Pathway
Pollard, V. W., Michael, W. M., Nakielny, S., Siomi, M. C., Wang, F., & Dreyfuss, G. (1996) · Cell · doi:10.1016/s0092-8674(00)80173-7 · Cited by 667 · see citing works
Levi, S., Luzzago, A., Cesareni, G., Cozzi, A., Franceschinelli, F., Albertini, A., & Arosio, P. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)81326-1 · Cited by 378 · see citing works
Wang, Z., & Brown, D. D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.24.11505 · Cited by 352 · see citing works
Cell killing and DNA damage by hydrogen peroxide are mediated by intracellular iron
Filho, A. C. M., Hoffmann, M. E., & Meneghini, R. (1984) · Biochemical Journal · doi:10.1042/bj2180273 · Cited by 337 · see citing works
Hempstead, P. D., Yewdall, S. J., Fernie, A. R., Lawson, D. M., Artymiuk, P. J., Rice, D. W., Ford, G. C., & Harrison, P. M. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.0970 · Cited by 318 · see citing works
Evidence that pyrimidine dimers in DNA can give rise to tumors.
Hart, R. W., Setlow, R. B., & Woodhead, A. D. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5574 · Cited by 257 · see citing works
Fluorescence microphotolysis to measure nucleocytoplasmic transport and intracellular mobility
Peters, R. (1986) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(86)90003-1 · Cited by 249 · see citing works
Epitope Mapping by Label-Free Biomolecular Interaction Analysis
Malmqvist, M. (1996) · Methods · doi:10.1006/meth.1996.0060 · Cited by 223 · see citing works
Iron and oxygen radicals in brain
Gutteridge, J. M. C. (1992) · Annals of Neurology · doi:10.1002/ana.410320705 · Cited by 191 · see citing works
THE CORNEA-SCIENTIFIC FOUNDATIONS AND CLINICAL PRACTICE
Smolin, G., & Thoft, R. A. (1983) · Optometry and Vision Science · doi:10.1097/00006324-198311000-00014 · Cited by 182 · see citing works
Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions
Henle, E. S., Luo, Y., Gassmann, W., & Linn, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21177 · Cited by 175 · see citing works
Iron is the intracellular metal involved in the production of DNA damage by oxygen radicals
Mello-Filho, A. C., & Meneghini, R. (1991) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(91)90220-i · Cited by 159 · see citing works
Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions
Luo, Y., Henle, E. S., & Linn, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21167 · Cited by 159 · see citing works
In or out? Regulating nuclear transport
Hood, J. K., & Silver, P. A. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80032-5 · Cited by 137 · see citing works
Nuclear Ferritin Protects DNA From UV Damage in Corneal Epithelial Cells
Cai, C. X., Birk, D. E., & Linsenmayer, T. F. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.5.1037 · Cited by 122 · see citing works
Self-citationTransportin: Nuclear Transport Receptor of a Novel Nuclear Protein Import Pathway
Nakielny, S., Siomi, M. C., Siomi, H., Michael, W. M., Pollard, V. W., & Dreyfuss, G. (1996) · Experimental Cell Research · doi:10.1006/excr.1996.0369 · Cited by 115 · see citing works
Southwood, C. M., Downs, K. M., & Bieker, J. J. (1996) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199607)206:3 · Cited by 108 · see citing works
Self-citationMutational analysis of the channel and loop sequences of human ferritin H-chain
Levi, S., Luzzago, A., Franceschinelli, F., Santambrogio, P., Cesareni, G., & Arosio, P. (1989) · Biochemical Journal · doi:10.1042/bj2640381 · Cited by 104 · see citing works
Briggs, L. J., Stein, D., Goltz, J. S., Corrigan, V. C., Efthymiadis, A., Hübner, S., & Jans, D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.35.22745 · Cited by 98 · see citing works
Kasetsuwan, N. (1999) · Archives of Ophthalmology · doi:10.1001/archopht.117.5.649 · Cited by 85 · see citing works
Structure and expression of the chicken ferritin H-subunit gene.
Stevens, P. W., Dodgson, J. B., & Engel, J. D. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.5.1751 · Cited by 84 · see citing works
Broxmeyer, H. E., Cooper, S. H., Levi, S., & Arosio, P. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.3.770 · Cited by 81 · see citing works
The Cornea: Scientific Foundations and Clinical Practice
Maguire, L. J. (1988) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(12)64878-2 · Cited by 74 · see citing works
Gerl, M., Jaenicke, R., Smith, J. M., & Harrison, P. M. (1988) · Biochemistry · doi:10.1021/bi00411a027 · Cited by 66 · see citing works
Effects of modifications near the 2-, 3- and 4-fold symmetry axes on human ferritin renaturation
Santambrogio, P., Pinto, P., Levi, S., Cozzi, A., Rovida, E., Albertini, A., Artymiuk, P. J., Harrison, P. M., & Arosio, P. (1997) · Biochemical Journal · doi:10.1042/bj3220461 · Cited by 55 · see citing works
Ferritin Is a Developmentally Regulated Nuclear Protein of Avian Corneal Epithelial Cells
Cai, C. X., Birk, D. E., & Linsenmayer, T. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.19.12831 · Cited by 55 · see citing works
Self-citationTransient overexpression of human H- and L-ferritin chains in COS cells
Corsi, B., Perrone, F., Bourgeois, M., Beaumont, C., Panzeri, C., Cozzi, A., Sangregorio, R., Santambrogio, P., Albertini, A., Arosio, P., et al. (1998) · Biochemical Journal · doi:10.1042/bj3300315 · Cited by 43 · see citing works
Nuclear translocation of ferritin in corneal epithelial cells
Cai, C. X., & Linsenmayer, T. F. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.12.2327 · Cited by 41 · see citing works
Self-citationPassaniti, A., & Roth, T. F. (1989) · Biochemical Journal · doi:10.1042/bj2580413 · Cited by 39 · see citing works
Lavoie, D. J., Ishikawa, K., & Listowsky, I. (1978) · Biochemistry · doi:10.1021/bi00618a019 · Cited by 39 · see citing works
DNA damage and repair in rabbit lens epithelial cells following UVA radiation
Sidjanin, D. J., Zigman, S., & Reddan, J. R. (1993) · Current Eye Research · doi:10.3109/02713689309020382 · Cited by 38 · see citing works
Rubin, B. S., Lee, C. E., Ohtomo, M., & King, J. C. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00879-2 · Cited by 34 · see citing works
Specific repression of β-globin promoter activity by nuclear ferritin
Broyles, R. H., Belegu, V., DeWitt, C. R., Shah, S. N., Stewart, C. A., Pye, Q. N., & Floyd, R. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151147098 · Cited by 32 · see citing works
Pountney, D., Trugnan, G., Bourgeois, M., & Beaumont, C. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.6.825 · Cited by 27 · see citing works
Monoclonal antibodies against developmentally regulated corneal antigens
Zak, N. B., & Linsenmayer, T. F. (1983) · Developmental Biology · doi:10.1016/0012-1606(83)90287-7 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 5
- Hart, R. W., Setlow, R. B., and Woodhead, A. D. (1977) Proc. Natl. Acad. Sci.
- Broxmeyer, H. E., Cooper, S., Levi, S., and Arosio, P. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 770 -774
- Wang, Z., and Brown, D. D. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 11505-11509
- Alexandrov, N. N., Nussinov, R., and Zimmer, R. M. (1995) in Pacific Sympo- sium on Biocomputing, Kohala Coast, HI, January 3-6, 1996 (Hunter, L., and Klein, T. E., eds) pp. 53-72, World Scientific Publishing Co., Singapore
- Broyles, R. H., Belegu, V., DeWitt, C. R., Shah, S. N., Stewart, C. A., Pye, Q. N., and Floyd, R. A. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 9145-9150
Cited by
Sorted by citations
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Arosio, P., Ingrassia, R., & Cavadini, P. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.09.004 · Cited by 886 · see citing works
Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
Chemistry and biology of ferritin
Plays, M., Müller, S., & Rodriguez, R. (2021) · Metallomics · doi:10.1093/mtomcs/mfab021 · Cited by 232 · see citing works
Vidal, R., Ghetti, B. F., Takao, M., Brefel‐Courbon, C., Uro‐Coste, E., Glazier, B. S., Siani, V., Benson, M. D., Calvas, P., Miravalle, L., et al. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.4.363 · Cited by 161 · see citing works
Li, R., Luo, C., Mines, M. A., Zhang, J., & Fan, G.-H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607266200 · Cited by 129 · see citing works
Iron homeostasis and eye disease
Loh, A. R., Hadziahmetovic, M., & Dunaief, J. L. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.11.001 · Cited by 125 · see citing works
Nuclear ferritin: A new role for ferritin in cell biology
Alkhateeb, A. A., & Connor, J. R. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2010.03.017 · Cited by 125 · see citing works
The importance of eukaryotic ferritins in iron handling and cytoprotection
Arosio, P., Carmona, F., Gozzelino, R., Maccarinelli, F., & Poli, M. (2015) · Biochemical Journal · doi:10.1042/bj20150787 · Cited by 104 · see citing works
Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress
Woulfe, J. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00819.x · Cited by 88 · see citing works
Storr, H. L., Kind, B., Parfitt, D. A., Chapple, J. P., Lorenz, M., Koehler, K., Huebner, A., & Clark, A. J. L. (2009) · Molecular Endocrinology · doi:10.1210/me.2009-0056 · Cited by 84 · see citing works
Characterization of nuclear ferritin and mechanism of translocation
SURGULADZE, N., PATTON, S., COZZI, A., FRIED, M. G., & CONNOR, J. R. (2005) · Biochemical Journal · doi:10.1042/bj20041853 · Cited by 81 · see citing works
Iron metabolism in the eye: A review
Goralska, M., Ferrell, J., Harned, J., Lall, M. M., Nagar, S., Fleisher, L. N., & McGahan, M. C. (2008) · Experimental Eye Research · doi:10.1016/j.exer.2008.10.026 · Cited by 47 · see citing works
Linsenmayer, T. F., Cai, C. X., Millholland, J. M., Beazley, K. E., & Fitch, J. M. (2004) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2004.08.004 · Cited by 37 · see citing works
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Domenico, I. D., Vaughn, M. B., Paradkar, P. N., Lo, E., Ward, D. M., & Kaplan, J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2010.12.003 · Cited by 24 · see citing works
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Infante, A. A., Infante, D., Chan, M.-C., How, P.-C., Kutschera, W., Linhartová, I., Müllner, E. W., Wiche, G., & Propst, F. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.02.021 · Cited by 19 · see citing works
Sabbir, M. G., Taylor, C. G., & Zahradka, P. C. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118763 · Cited by 19 · see citing works
Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis
Fox, T. P., Gotlinger, K. H., Dunn, M. W., Lee, O. L., Milman, T., Zaidman, G. W., Schwartzman, M. L., & Bellner, L. (2013) · Cornea · doi:10.1097/ico.0b013e3182936915 · Cited by 18 · see citing works
Kuo, H. C., Smith, J. J., Lis, A., Zhao, L., Gonsiorek, E. A., Zhou, X., Higgins, D. M., Roth, J. A., Garrick, M. D., & Garrick, L. M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20112 · Cited by 15 · see citing works
Beazley, K. E., Nurminskaya, M., Talbot, C. J., & Linsenmayer, T. F. (2008) · Developmental Dynamics · doi:10.1002/dvdy.21691 · Cited by 13 · see citing works
Self-citationStorr, H. L., Kind, B., Parfitt, D. A., Chapple, J. P., Lorenz, M., Koehler, K., Huebner, A., & Clark, A. J. L. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.94.11.9995 · Cited by 12 · see citing works
Supramolecular Protein Assemblies in the Nucleus of Human Cells
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Nurminskaya, M. V., Talbot, C. J., Nurminsky, D. I., Beazley, K. E., & Linsenmayer, T. F. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3170 · Cited by 10 · see citing works
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Beazley, K. E., Nurminskaya, M., & Linsenmayer, T. F. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22154 · Cited by 9 · see citing works
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Self-citationBeazley, K. E., Canner, J. P., & Linsenmayer, T. F. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.07.007 · Cited by 7 · see citing works
Self-citationSümer, F., Kızılkaya, B., Yıldız, E., Satılmaz, M. F., & Suveys, A. (2025) · Scientific Reports · doi:10.1038/s41598-025-93800-0 · Cited by 3 · see citing works
Linsenmayer, T. F., Beazley, K. E., Cai, C. X., Canner, J. P., Fitch, J. M., Kubilus, J. K., Millholland, J. M., Nurminskaya, M., Talbot, C. J., & Zak, N. B. (2014) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-1-4939-1935-2_3 · Cited by 3 · see citing works
Self-citation
- Authors
- Millholland, J. M., Fitch, J. M., Cai, C. X., Gibney, E. P., Beazley, K. E., & Linsenmayer, T. F.
- Affiliations
- Tufts University (US)
- Corresponding author
- Linsenmayer, Thomas F.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 278
- Issue
- 26
- Pages
- 23963-23970
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2159449353
- Cited by
- 30
- References
- 44
- Citations by year
- 2025: 1 · 2021: 1 · 2020: 1 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (EY13127, R01EY013127)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- ferritin, nuclear transport, corneal epithelial cells, nuclear localization signal, developmental regulation
- MeSH terms
- Animals, Base Sequence, Carrier Proteins, Chick Embryo, Ferritins, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Transfection, Protein Structure, Tertiary, DNA, Complementary, COS Cells, Epithelium, Corneal, Nuclear Localization Signals, Active Transport, Cell Nucleus, Membrane Transport Proteins
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