Lats2 is an essential mitotic regulator required for the coordination of cell division
Lats2 is an essential mitotic regulator required for the coordination of cell division
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DOI：
10.1074/jbc.m608562200
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发表时间：
2007-06-29
影响因子：
4.8
通讯作者：
Nojima, Hiroshi
中科院分区：
文献类型：
--
作者：
Yabuta, Norikazu;Okada, Nobuhiro;Nojima, Hiroshi
肿瘤抑制因子Lats2是保守的Dbf2激酶家族的成员。它定位于中心体，并与细胞周期和凋亡的调节有关。然而，这种激酶的体内功能仍不清楚。在这里，我们表明，在小鼠中完全破坏Lats2编码基因会导致神经系统发育缺陷和胚胎死亡。此外，来自LATS 2基因敲除胚胎的突变体细胞表现出有丝分裂缺陷，包括中心体断裂和胞质分裂缺陷，随后是核增大和多核化。我们发现，Mob1家族，有丝分裂出口的调节器，与Lats2相关联，以诱导其激活。我们还表明，完全LATS 2基因敲除细胞表现出加速退出有丝分裂和显着下调的关键有丝分裂调节。这些结果表明，Lats2在协调准确的胞质分裂完成中起着重要的有丝分裂作用，控制着其他有丝分裂调节因子的稳定。
Tumor suppressor Lats2 is a member of the conserved Dbf2 kinase family. It localizes to the centrosome and has been implicated in regulation of the cell cycle and apoptosis. However, the in vivo function of this kinase remains unclear. Here, we show that complete disruption of the gene encoding Lats2 in mice causes developmental defects in the nervous system and embryonic lethality. Furthermore, mutant cells derived from total LATS2-knock-out embryos exhibit mitotic defects including centrosome fragmentation and cytokinesis defects, followed by nuclear enlargement and multinucleation. We show that the Mob1 family, a regulator of mitotic exit, associates with Lats2 to induce its activation. We also show that the complete LATS2-knock-out cells exhibit an acceleration of exit from mitosis and marked down-regulation of critical mitotic regulators. These results suggest that Lats2 plays an essential mitotic role in coordinating accurate cytokinesis completion, governing the stabilization of other mitotic regulators.