GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth |
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Authors: | Zhang Bicheng Huang Jun Li Hong-Liang Liu Ting Wang Yan-Yi Waterman Paul Mao Ai-Ping Xu Liang-Guo Zhai Zhonghe Liu Depei Marrack Philippa Shu Hong-Bing |
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Institution: | HHMI, National Jewish Medical and Research Center, Denver, CO 80206, USA. |
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Abstract: | Here, we report the identification of GIDE, a mitochondrially located E3 ubiquitin ligase. GIDE contains a C-terminal RING finger domain, which is mostly conserved with those of the IAP family members and is required for GIDE's E3 ligase activity. Overexpression of GIDE induces apoptosis via a pathway involving activation of caspases, since caspase inhibitors, XIAP and an inactive mutant of caspase-9 block GIDE-induced apoptosis. GIDE also activates JNK, and blockage of JNK activation inhibits GIDE-induced release of cytochrome c and Smac as well as apoptosis, suggesting that JNK activation precedes release of cytochrome c and Smac and is required for GIDE-induced apoptosis. These pro-apoptotic properties of GIDE require its E3 ligase activity. When somewhat over- or underexpressed, GIDE slows or accelerates cell growth, respectively. These pro-apoptotic or growth inhibition effects of GIDE may account for its absence in tumor cells. |
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Keywords: | GIDE apoptosis E3 ligase mitochondria caspase JNK |
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