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J. Biol. Chem., Vol. 277, Issue 15, 12901-12905, April 12, 2002
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,
From the Laboratory of Molecular Immunology, Felsenstein Medical
Research Center, Sackler School of Medicine, Tel Aviv University,
Rabin Medical Center, Petah Tikva 49100, Israel
Ferritin is a ubiquitous iron storage protein
existing in multiple isoforms composed of 24 heavy and light chain
subunits. We describe here a third ferritin-related subunit cloned from human placenta cDNA library and named PLIF (placental
immunomodulatory ferritin). The PLIF coding region is composed of
ferritin heavy chain (FTH) sequence lacking the 65 C-terminal amino
acids, which are substituted with a novel 48 amino acid domain (C48).
In contrast to FTH, PLIF mRNA does not include the iron response
element in the 5'-untranslated region, suggesting that PLIF
synthesis is not regulated by iron. The linkage between the FTH and C48
domains created a restriction site for EcoRI. PLIF protein
was found to localize in syncytiotrophoblasts of placentas (8 weeks of
gestation) at the fetal-maternal interface. Increased levels of
PLIF transcript and protein were also detected in the breast carcinoma
cell lines T47D and MCF-7 but not in the benign corresponding cell line
HBL-100. In vitro, PLIF was shown to down-modulate mixed
lymphocyte reactions and to inhibit the proliferation of peripheral
blood mononuclear cells stimulated with OKT3. The accumulated data
indicate that PLIF is an embryonic immune factor involved in
down-modulating the maternal immune recognition of the embryo toward
anergy. This mechanism may have been adapted by breast cancer cells
over expressing PLIF.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY033611.
To whom correspondence should be addressed. Tel.: 972-3-937-7507;
Fax: 972-3-924-7019; E-mail: hmoroz@post.tau.ac.il.
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