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Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells
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Title: | Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells |
Authors: | Tsukamoto, Takashi Browse this author | Li, Xianglan Browse this author | Morita, Hiromi Browse this author →KAKEN DB | Minowa, Takashi Browse this author →KAKEN DB | Aizawa, Tomoyasu Browse this author →KAKEN DB | Hanagata, Nobutaka Browse this author →KAKEN DB | Demura, Makoto Browse this author →KAKEN DB |
Issue Date: | 18-Sep-2013 |
Publisher: | Public library science |
Journal Title: | Plos one |
Volume: | 8 |
Issue: | 9 |
Start Page: | 1 |
End Page: | 13 |
Publisher DOI: | 10.1371/journal.pone.0075831 |
Abstract: | Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection. In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmitoylation, plays a crucial role for the antiviral activity. IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop. Because these cysteines are well conserved in the mammalian IFITM family proteins, the S-palmitoylation on these cysteines is significant for their functions. IFITM5 is another IFITM family protein and interacts with the FK506-binding protein 11 (FKBP11) to form a higher-order complex in osteoblast cells, which induces the expression of immunologically relevant genes. In this study, we investigated the role played by S-palmitoylation of IFITM5 in its interaction with FKBP11 in the cells, because this interaction is a key process for the gene expression. Our investigations using an established reporter, 17-octadecynoic acid (17-ODYA), and an inhibitor for the S-palmitoylation, 2-bromopalmitic acid (2BP), revealed that IFITM5 was S-palmitoylated in addition to IFITM3. Specifically, we found that cysteine residues in the TM1 domain and in the CP loop were S-palmitoylated in IFITM5. Then, we revealed by immunoprecipitation and western blot analyses that the interaction of IFITM5 with FKBP11 was inhibited in the presence of 2BP. The mutant lacking the S-palmitoylation site in the TM1 domain lost the interaction with FKBP11. These results indicate that the S-palmitoylation on IFITM5 promotes the interaction with FKBP11. Finally, we investigated bone nodule formation in osteoblast cells in the presence of 2BP, because IFITM5 was originally identified as a bone formation factor. The experiment resulted in a morphological aberration of the bone nodule. This also indicated that the S-palmitoylation contributes to bone formation. |
Rights: | http://creativecommons.org/licenses/by/3.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/53593 |
Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 出村 誠
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