Mouse emi1 has an essential function in mitotic progression during early embryogenesis
Mouse emi1 has an essential function in mitotic progression during early embryogenesis
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DOI：
10.1128/mcb.00043-06
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发表时间：
2006-07-01
影响因子：
5.3
通讯作者：
Lim, Dae-Sik
中科院分区：
文献类型：
--
作者：
Lee, Ho;Lee, Dong Jun;Lim, Dae-Sik
为了成功进入有丝分裂和纺锤体组装，有丝分裂促进因子在 G(2)/M 过渡阶段被激活，然后刺激后期促进复合物 (APC)（一种 E3 泛素连接酶），以指导几个关键有丝分裂调节因子的有序破坏。鉴于抑制 APC 活性对于防止过早或不正确的泛素化和底物破坏非常重要，因此已经研究了几种调节剂及其调节机制。 Emi1 是一种早期有丝分裂抑制剂，是这些调节因子之一。在这里，我们通过分析 Emi1 缺陷胚胎表明，Emi1 对于早期胚胎发生过程中精确的有丝分裂进展至关重要。由于植入前发育缺陷，Emi1(-/-) 胚胎被发现是致命的。细胞增殖似乎正常，但胚胎分裂期间有丝分裂进展严重缺陷。此外，在 Emi1 突变细胞中经常观察到多极纺锤体和错位染色体，这可能是由于 APC 过早激活所致。我们的结果总体表明 Emi1 的晚期前期检查点功能对于准确的有丝分裂进展和胚胎活力至关重要。
For successful mitotic entry and spindle assembly, mitosis-promoting factors are activated at the G(2)/M transition stage, followed by stimulation of the anaphase-promoting complex (APC), an E3 ubiquitin ligase, to direct the ordered destruction of several critical mitotic regulators. Given that inhibition of APC activity is important for preventing premature or improper ubiquitination and destruction of substrates, several modulators and their regulation mechanisms have been studied. Emi1, an early mitotic inhibitor, is one of these regulatory factors. Here we show, by analyzing Emi1-deficient embryos, that Emi1 is essential for precise mitotic progression during early embryogenesis. Emi1(-/-) embryos were found to be lethal due to a defect in preimplantation development. Cell proliferation appeared to be normal, but mitotic progression was severely defective during embryonic cleavage. Moreover, multipolar spindles and misaligned chromosomes were frequently observed in Emi1 mutant cells, possibly due to premature APC activation. Our results collectively suggest that the late prophase checkpoint function of Emi1 is essential for accurate mitotic progression and embryonic viability.