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Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury
| 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)
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Submitter: 上原 孝
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