GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth

• Published in: Cell research Vol. 18; no. 9; pp. 900 - 910
• Main 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2008
• Subjects: Amino Acid Sequence; Animals; Apoptosis - drug effects; Caspase Inhibitors; Cell Line; Cell Proliferation - drug effects; E3连接酶; Enzyme Activation - drug effects; Gene Expression Profiling; GIDE; Humans; Inhibitor of Apoptosis Proteins - metabolism; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinases - metabolism; Mice; Mitochondria - drug effects; Mitochondria - enzymology; Molecular Sequence Data; NIH 3T3 Cells; Protease Inhibitors - pharmacology; Protein Transport - drug effects; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination - drug effects; 线粒体; 细胞凋亡
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2008.75

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 lAP 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.