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Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury

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タイトル: Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury
著者: Tsuruma, Kazuhiro 著作を一覧する
Nakagawa, Tadashi 著作を一覧する
Morimoto, Nobutaka 著作を一覧する
Minami, Masabumi 著作を一覧する
Hara, Hideaki 著作を一覧する
Uehara, Takashi 著作を一覧する
Nomura, Yasuyuki 著作を一覧する
キーワード: signaling complex disc
cytochrome-c release
kappa-B activation
cell-death
disulfide isomerase
sh-sy5y cells
receptro
mitochondria
protease
caspases
発行日: 2006年 4月21日
出版者: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY
誌名: Journal of biological chemistry
巻: 281
号: 16
開始ページ: 11397
終了ページ: 11404
出版社 DOI: 10.1074/jbcM510597200
抄録: Caspases are divided into two classes: initiator caspases, which include caspase-8 and - 9 and possess long prodomains, and effector caspases, which include caspase-3 and - 7 and possess short prodomains. Recently, we demonstrated that glucocorticoid modulatory element-binding protein 1( GMEB1) interacts with the prodomain of procaspase-2, thereby disrupting its autoactivation and the induction of apoptosis. Here we show that GMEB1 is also capable of binding to procaspase-8 and - 9. GMEB1 attenuated the Fas-mediated activation of these caspases and the subsequent apoptosis. The knockdown of endogenous GMEB1 using RNA interference revealed that cells with decreased GMEB1 expression are more sensitive to stress and undergo accelerated apoptosis. Transgenic mice expressing a neurospecific GMEB1 had smaller cerebral infarcts and less brain swelling than wildtype mice in response to transient focal ischemia. These results suggest that GMEB1 is an endogenous regulator that selectively binds to initiator procaspases and inhibits caspase-induced apoptosis
Rights: Copyright(c)2006 by the American Society for Biochemistry and Molecular Biology
Relation (URI): http://www.jbc.org/
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/8511
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 上原 孝

 

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