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Originally published In Press as doi:10.1074/jbc.M210050200 on April 15, 2003

J. Biol. Chem., Vol. 278, Issue 26, 23963-23970, June 27, 2003
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Ferritoid, a Tissue-specific Nuclear Transport Protein for Ferritin in Corneal Epithelial Cells*

John M. Millholland {ddagger}, John M. Fitch, Cindy X. Cai, Eileen P. Gibney, Kelly E. Beazley and Thomas F. Linsenmayer §

From the Department of Anatomy and Cellular Biology, Tufts University Medical School, Boston, Massachusetts 02111

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 ~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).


Received for publication, October 1, 2002 , and in revised form, April 3, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to GenBankTM/EBI Data Bank with the accession number(s) AF447376.

* This work was supported by National Institutes of Health Grant EY 13127 (to T. F. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} Present address: Department of Pathology and Laboratory Medicine, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104.

§ To whom correspondence should be addressed: Dept. of Anatomy and Cellular Biology, Tufts University Medical School, Jaharis 329, 150 Harrison Ave., Boston, MA 02111. Tel.: 617-636-6695; Fax: 617-636-6536; E-mail: thomas.linsenmayer{at}tufts.edu.


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[Abstract] [Full Text] [PDF]




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