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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
Ferritoid, a Tissue-specific Nuclear Transport Protein for Ferritin in Corneal Epithelial Cells*
John M. Millholland ,
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.
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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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
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