PLIF, a novel human ferritin subunit from placenta with immunosuppressive activity.
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.
Moroz
Chaya
C
Laboratory of Molecular Immunology, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Rabin Medical Center, Petah Tikva 49100, Israel. hmoroz@post.tau.ac.il
Traub
Leonid
L
Maymon
Ron
R
Zahalka
Muayad A
MA
D000595:Amino Acid Sequence; D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D005293:Ferritins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D010920:Placenta / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology
D018076:DNA, Complementary; D011257:Pregnancy Proteins; D005293:Ferritins; C454461:FTH1 protein, human; D010088:Oxidoreductases