{
   "sha": "0d8784d230453109b9340461f2692f0f2d048927",
   "source_x": "PMC",
   "title": "Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells",
   "doi": "http://dx.doi.org/10.1371/journal.pone.0075831",
   "pmcid": "PMC3776769",
   "pubmed_id": "24058703",
   "license": "CC BY",
   "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.",
   "publish_time": "2013 Sep 18",
   "authors": [
      "['Tsukamoto, Takashi', 'Li, Xianglan', 'Morita, Hiromi', 'Minowa, Takashi', 'Aizawa, Tomoyasu', 'Hanagata, Nobutaka', 'Demura, Makoto']"
   ],
   "journal": "PLoS One",
   "has_full_text": "True",
   "id": "0d8784d230453109b9340461f2692f0f2d048927",
   "fhir_link": "Commercial/0d8784d230453109b9340461f2692f0f2d048927"
}