Immunophilin FKBP38, an inherent inhibitor of calcineurin, 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

5 引用 (Scopus)

抄録

Various apoptotic stimuli induce mitochondrial dysfunction. Bcl-2 and Bcl-xL antagonize apoptosis by blocking the release of caspase activators such as cytochrome c from mitochondria. We demonstrated that FKBP38, a member of the immunophilin family, interacts and targets these anti-apoptotic proteins Bcl-2 and Bcl-xL, thereby assisting them in their pro-survival role. FKBP38 is specifically localized on mitochondria, at which FKBP38 is colocalized with Bcl-2 and Bcl-xL. Expression of exogenous FKBP38 promotes mitochondrial targeting of Bcl-2 and Bcl-xL, while dominant-negative FKBP38 or siRNA of FKBP38 disturbs their localization. On the other hand, unlike FKBP12, FKBP38 inhibits serine/threonine phosphatase calcineurin in an FK506-independent manner. Overexpression of FKBP38 inhibits apoptosis, while expression of dominant-negative FKBP38 or depletion of endogenous FKBP38 increases the sensitivity for apoptosis. Thus, FKBP38 has unique features among members of the immunophilin family.

元の言語英語
ページ(範囲)405-412
ページ数8
ジャーナルNippon rinsho. Japanese journal of clinical medicine
62
発行部数2
出版物ステータス出版済み - 1 1 2004

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Immunophilins
Mitochondria
Apoptosis
Tacrolimus Binding Protein 1A
Apoptosis Regulatory Proteins
Calcineurin
Phosphoprotein Phosphatases
Tacrolimus
Caspases
Cytochromes c
Small Interfering RNA
Calcineurin Inhibitors

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

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

:: Nippon rinsho. Japanese journal of clinical medicine, 巻 62, 番号 2, 01.01.2004, p. 405-412.

研究成果: ジャーナルへの寄稿評論記事

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title = "Immunophilin FKBP38, an inherent inhibitor of calcineurin, targets Bcl-2 to mitochondria and inhibits apoptosis",
abstract = "Various apoptotic stimuli induce mitochondrial dysfunction. Bcl-2 and Bcl-xL antagonize apoptosis by blocking the release of caspase activators such as cytochrome c from mitochondria. We demonstrated that FKBP38, a member of the immunophilin family, interacts and targets these anti-apoptotic proteins Bcl-2 and Bcl-xL, thereby assisting them in their pro-survival role. FKBP38 is specifically localized on mitochondria, at which FKBP38 is colocalized with Bcl-2 and Bcl-xL. Expression of exogenous FKBP38 promotes mitochondrial targeting of Bcl-2 and Bcl-xL, while dominant-negative FKBP38 or siRNA of FKBP38 disturbs their localization. On the other hand, unlike FKBP12, FKBP38 inhibits serine/threonine phosphatase calcineurin in an FK506-independent manner. Overexpression of FKBP38 inhibits apoptosis, while expression of dominant-negative FKBP38 or depletion of endogenous FKBP38 increases the sensitivity for apoptosis. Thus, FKBP38 has unique features among members of the immunophilin family.",
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T1 - Immunophilin FKBP38, an inherent inhibitor of calcineurin, targets Bcl-2 to mitochondria and inhibits apoptosis

AU - Shirane, Michiko

AU - Nakayama, Keiichi

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N2 - Various apoptotic stimuli induce mitochondrial dysfunction. Bcl-2 and Bcl-xL antagonize apoptosis by blocking the release of caspase activators such as cytochrome c from mitochondria. We demonstrated that FKBP38, a member of the immunophilin family, interacts and targets these anti-apoptotic proteins Bcl-2 and Bcl-xL, thereby assisting them in their pro-survival role. FKBP38 is specifically localized on mitochondria, at which FKBP38 is colocalized with Bcl-2 and Bcl-xL. Expression of exogenous FKBP38 promotes mitochondrial targeting of Bcl-2 and Bcl-xL, while dominant-negative FKBP38 or siRNA of FKBP38 disturbs their localization. On the other hand, unlike FKBP12, FKBP38 inhibits serine/threonine phosphatase calcineurin in an FK506-independent manner. Overexpression of FKBP38 inhibits apoptosis, while expression of dominant-negative FKBP38 or depletion of endogenous FKBP38 increases the sensitivity for apoptosis. Thus, FKBP38 has unique features among members of the immunophilin family.

AB - Various apoptotic stimuli induce mitochondrial dysfunction. Bcl-2 and Bcl-xL antagonize apoptosis by blocking the release of caspase activators such as cytochrome c from mitochondria. We demonstrated that FKBP38, a member of the immunophilin family, interacts and targets these anti-apoptotic proteins Bcl-2 and Bcl-xL, thereby assisting them in their pro-survival role. FKBP38 is specifically localized on mitochondria, at which FKBP38 is colocalized with Bcl-2 and Bcl-xL. Expression of exogenous FKBP38 promotes mitochondrial targeting of Bcl-2 and Bcl-xL, while dominant-negative FKBP38 or siRNA of FKBP38 disturbs their localization. On the other hand, unlike FKBP12, FKBP38 inhibits serine/threonine phosphatase calcineurin in an FK506-independent manner. Overexpression of FKBP38 inhibits apoptosis, while expression of dominant-negative FKBP38 or depletion of endogenous FKBP38 increases the sensitivity for apoptosis. Thus, FKBP38 has unique features among members of the immunophilin family.

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