title: Ca2+/S100 proteins inhibit the interaction of FKBP38 with Bcl-2 and Hsp90.
abstract: FKBP38 (FK506-binding protein 38), a membrane-anchored TPR (tetratricopeptide repeat)-containing immunophilin, regulates signalling pathways such as cell survival, apoptosis, proliferation and metastasis. However, the mechanisms that regulate the activity of FKBP38 are, at present, poorly understood. We previously reported that Ca2+/S100 proteins directly associate with the TPR proteins, such as Hop [Hsp70 (heat-shock protein of 70 kDa)/Hsp90-organizing protein], kinesin-light chain, Tom70 (translocase of outer mitochondrial membrane 70), FKBP52, CyP40 (cyclophilin 40), CHIP (C-terminus of Hsc70-interacting protein) and PP5 (protein phosphatase 5), leading to the dissociation of the interactions of the TPR proteins with their target proteins. Therefore we have hypothesized that Ca2+/S100 proteins can interact with FKBP38 and regulate its function. In vitro binding studies demonstrated that S100A1, S100A2, S100A6, S100B and S100P specifically interact with FKBP38 and inhibit the interaction of FKBP38 with Bcl-2 and Hsp90. Overexpression of permanently active S100P in Huh-7 cells inhibited the interaction of FKBP38 with Bcl-2, resulting in the suppression of Bcl-2 stability. The association of the S100 proteins with FKBP38 provides a Ca2+-dependent regulatory mechanism of the FKBP38-mediated signalling pathways.
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimamoto
authors.affiliation: *Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: ‡Department of Cell Physiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Yamaguchi
authors.affiliation: §Department of Dermatology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: *Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokumitsu
authors.affiliation: *Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism / Q000502:physiology*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*
chemical_list: C471205:FKBP8 protein, human; D018841:HSP90 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D009418:S100 Proteins; D022021:Tacrolimus Binding Proteins; D002118:Calcium