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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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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/8511

Title: Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury
Authors: Tsuruma, Kazuhiro Browse this author
Nakagawa, Tadashi Browse this author
Morimoto, Nobutaka Browse this author
Minami, Masabumi Browse this author
Hara, Hideaki Browse this author
Uehara, Takashi Browse this author
Nomura, Yasuyuki Browse this author
Keywords: signaling complex disc
cytochrome-c release
kappa-B activation
cell-death
disulfide isomerase
sh-sy5y cells
receptro
mitochondria
protease
caspases
Issue Date: 21-Apr-2006
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY
Journal Title: Journal of biological chemistry
Volume: 281
Issue: 16
Start Page: 11397
End Page: 11404
Publisher DOI: 10.1074/jbcM510597200
Abstract: 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: http://www.jbc.org/
Type: article (author version)
URI: http://hdl.handle.net/2115/8511
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 上原 孝

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