title: Nuclear localization of magphinins, alternative splicing products of the human trophinin gene.
abstract: Human magphinin proteins are translation products of differentially spliced transcripts from the 5' region of the human trophinin gene (TRO), whose 3' region encodes trophinin, a unique cell adhesion molecule involved in human embryo implantation. Magphinins belong to the MAGE (melanoma-associated antigen) family, and a previous study of mouse magphinins showed their expression in male and female germ cells, suggesting a role in germ cell development. Here, we characterized the structure and subcellular localization of human magphinins. Confocal microscopy analysis of ectopically expressed magphinins revealed that magphinin-alpha and -beta localize in the cytoplasm, whereas magphinin-gamma lacking the peptide encoded by exon-3 is nuclear. Following Triton X-100 extraction, DNA digestion, and high salt extraction magphinin-gamma remained nuclear, suggesting strong association with the nuclear matrix. A series of magphinin-gamma deletion mutants were generated and assayed for localization, which showed that the N-terminal region of the MAGE homology domain is necessary for nuclear localization. When magphinin-gamma was expressed in NIH3T3 cells, cells underwent G1 arrest. These results suggest that human magphinin-gamma inhibits cell cycle progression through nuclear activity.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Aoyama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Akazawa
authors.forename: Kousuke
authors.initials: K
authors.lastname: Kasahara
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Higashiyama
authors.forename: Ikue
authors.initials: I
authors.lastname: Kikuchi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: Sakura
authors.initials: S
authors.lastname: Saburi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry* / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry* / Q000502:physiology; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D019913:Nuclear Localization Signals; C093649:TRO protein, human; C445321:trophinin, mouse