Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis
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- 23 December 2002
- journal article
- research article
- Published by Springer Nature in Nature Cell Biology
- Vol. 5 (1) , 28-37
- https://doi.org/10.1038/ncb894
Abstract
The mitochondrial localization of the membrane proteins Bcl-2 and Bcl-xL 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-xL 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-xL. 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-xL to mitochondria.Keywords
This publication has 49 references indexed in Scilit:
- Regulation of tumor necrosis factor cytotoxicity by calcineurinFEBS Letters, 2000
- Ca 2+ -Induced Apoptosis Through Calcineurin Dephosphorylation of BADScience, 1999
- muFKBP38: A novel murine immunophilin homolog differentially expressed in Schwannoma cells and central nervous system neuronsin vivoElectrophoresis, 1999
- Calcineurin and mitochondrial function in glutamate‐induced neuronal cell deathFEBS Letters, 1996
- Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complexNature, 1995
- Calcineurin functions in Ca(2+)-activated cell death in mammalian cells.The Journal of cell biology, 1995
- X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complexCell, 1995
- Isolation of a cDNA encoding a novel human FK506-binding protein homolog containing leucine zipper and tetratricopeptide repeat motifsGene, 1995
- Immunophilins mediate the neuroprotective effects of FK506 in focal cerebral ischaemiaNature, 1994
- Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexesCell, 1991