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首页> 外文期刊>Molecular and Cellular Biology >BRUCE, a Giant E2/E3 Ubiquitin Ligase and Inhibitor of Apoptosis Protein of the trans-Golgi Network, Is Required for Normal Placenta Development and Mouse Survival
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BRUCE, a Giant E2/E3 Ubiquitin Ligase and Inhibitor of Apoptosis Protein of the trans-Golgi Network, Is Required for Normal Placenta Development and Mouse Survival

机译：正常胎盘发育和小鼠生存所必需的布鲁斯，一种巨大的E2 / E3泛素连接酶和反式高尔基体网络的凋亡蛋白抑制剂。

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摘要

BRUCE is a highly conserved 528-kDa peripheral membrane protein of the trans-Golgi network. Owing to the presence of an N-terminal single baculovirus inhibitor repeat, BRUCE functions as an inhibitor of apoptosis protein and blocks apoptosis when overexpressed. In addition, due to the presence of a C-terminal ubiquitin-conjugating domain, BRUCE can covalently attach ubiquitin to substrates. Here we report the generation and characterization of BRUCE-deficient mice. Complete inactivation of the BRUCE gene resulted in perinatal lethality and growth retardation discernible after embryonic day 14. The growth defect is linked to impaired placental development and may be caused by insufficient oxygen and nutrient transfer across the placenta. Chorioallantoic placentation initiated normally, but the mutant placenta showed an impaired maturation of the labyrinth layer and a significant reduction of the spongiotrophoblast. No evidence for an elevated apoptosis rate was detectable in embryonic and extraembryonic tissues and in knockout fibroblasts. Thus, although BRUCE is broadly expressed in embryonic, extraembryonic, and adult mouse tissues, this bifunctional protein might play a unique role in normal trophoblast differentiation and embryonic survival.
机译：BRUCE是 trans -Golgi网络的高度保守的528 kDa外周膜蛋白。由于存在N端单个杆状病毒抑制剂重复序列，因此BRUCE可以作为凋亡蛋白的抑制剂，并在过表达时阻止凋亡。另外，由于存在C端泛素缀合结构域，因此BRUCE可以将泛素共价结合到底物上。在这里，我们报告 BRUCE 缺陷小鼠的产生和特征。胚胎第14天后， BRUCE 基因完全失活，导致围产期致死率和生长迟缓。生长缺陷与胎盘发育受损有关，可能是由于氧气和营养素在胎盘上的转移不足所致。绒毛囊胎正常开始，但突变胎盘显示迷宫层成熟受损和海绵滋养细胞显着减少。在胚胎和胚外组织以及基因敲除的成纤维细胞中均未检测到凋亡率升高的证据。因此，尽管BRUCE在胚胎，胚外和成年小鼠组织中广泛表达，但这种双功能蛋白可能在正常的滋养细胞分化和胚胎存活中发挥独特的作用。

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