title: Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis.
abstract: The mitochondrial localization of the membrane proteins Bcl-2 and Bcl-x(L) is essential for their anti-apoptotic function. Here we show that mitochondrial FK506-binding protein 38 (FKBP38), unlike FKBP12, binds to and inhibits calcineurin in the absence of the immunosuppressant FK506, suggesting that FKBP38 is an inherent inhibitor of this phosphatase. FKBP38 is associated with Bcl-2 and Bcl-x(L) in immunoprecipitation assays and colocalizes with these proteins in mitochondria; in addition, the expression of FKBP38 mutant proteins induces a marked redistribution of Bcl-2 and Bcl-x(L). Overexpression of FKBP38 blocks apoptosis, whereas functional inhibition of this protein by a dominant-negative mutant or by RNA interference promotes apoptosis. Thus, FKBP38 might function to inhibit apoptosis by anchoring Bcl-2 and Bcl-x(L) to mitochondria.
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shirane
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D065095:Calcineurin Inhibitors; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000502:physiology*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D014162:Transfection; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D065095:Calcineurin Inhibitors; C471205:FKBP8 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D051020:bcl-X Protein; D022021:Tacrolimus Binding Proteins