Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function
Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function
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DOI：
10.1038/ncb1159
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发表时间：
2004-09-01
影响因子：
21.3
通讯作者：
Naito, M
中科院分区：
文献类型：
--
作者：
Hao, YY;Sekine, K;Naito, M
Apollon（也称为布鲁斯或BIRC 6）是一种分别在氨基和羧基末端含有杆状病毒IAP重复（BIR）和泛素缀合酶（UBC）结构域的大蛋白。Apollon抑制细胞凋亡，但其分子和生理功能尚不清楚。在这里，我们报告说，阿波罗结合，泛素化和促进蛋白酶体降解的SMAC和caspase-9，这两者都含有IAP结合基序。在小鼠中靶向破坏Apollon导致胚胎和新生儿死亡。值得注意的是，SMAC在Apollon缺陷细胞中诱导凋亡，但在Apollon表达细胞中不诱导凋亡。此外，IAP结合基序的SMAC是必需的，以诱导凋亡的阿波罗缺陷细胞。这些结果表明，Apollon在防止SMAC诱导的细胞凋亡中具有重要功能。
Apollon ( also known as BRUCE or BIRC6) is a large protein containing baculoviral-IAP- repeat (BIR) and ubiquitin-conjugating enzyme (UBC) domains at the amino- and carboxy termini, respectively. Apollon inhibits apoptosis, but its molecular and physiological function remains unclear. Here we report that Apollon binds to, ubiquitinates and facilitates proteasomal degradation of SMAC and caspase-9, which both contain IAP-binding motifs. Targeted disruption of Apollon in mice caused embryonic and neonatal lethality. Notably, SMAC induced apoptosis in Apollon-deficient cells, but not in Apollon-expressing cells. Furthermore, the IAP-binding motif of SMAC was required to induce apoptosis in Apollon-deficient cells. These results suggest that Apollon has an essential function in preventing SMAC-induced apoptosis.