Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis

Michiko Shirane, Keiichi Nakayama

研究成果: ジャーナルへの寄稿評論記事

217 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)28-37
ページ数10
ジャーナルNature Cell Biology
5
発行部数1
DOI
出版物ステータス出版済み - 1 1 2003

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Tacrolimus Binding Proteins
Mitochondria
Apoptosis
Tacrolimus Binding Protein 1A
Calcineurin
Mitochondrial Membranes
Tacrolimus
Mutant Proteins
Immunosuppressive Agents
RNA Interference
Phosphoric Monoester Hydrolases
Immunoprecipitation
Calcineurin Inhibitors
Membrane Proteins
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology

これを引用

Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis. / Shirane, Michiko; Nakayama, Keiichi.

:: Nature Cell Biology, 巻 5, 番号 1, 01.01.2003, p. 28-37.

研究成果: ジャーナルへの寄稿評論記事

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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.",
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