The Kinase Activity of Drosophila BubR1 Is Required for Insulin Signaling-Dependent Stem Cell Maintenance
The Kinase Activity of Drosophila BubR1 Is Required for Insulin Signaling-Dependent Stem Cell Maintenance
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果蝇 BubR1 的激酶活性是胰岛素信号依赖性干细胞维持所必需的
DOI：
10.1016/j.celrep.2020.107794
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发表时间：
2020-06-23
期刊：
影响因子：
8.8
通讯作者：
Yuan，Kai
中科院分区：
文献类型：
--
作者：
Tang，Ruijun;Jiang，Zhenghui;Yuan，Kai
作为有丝分裂检查点复合物的核心组分，BubR 1具有分子功能的模块化组织，在N末端具有KEN盒和其他基序，抑制后期促进复合物/细胞周期体，在C末端具有激酶结构域，其功能仍然不稳定，特别是在生物体水平。我们在果蝇基因组中产生敲入BubR 1突变，分别破坏KEN盒和激酶结构域。所有的突变体都是同源活的和可育的，并且在有丝分裂过程中没有显示出缺陷。没有激酶活性的突变体具有增加的寿命和与减弱的胰岛素信号传导相关的表型变化，包括细胞膜上InR减少，PI 3 K和AKT活性减弱，以及dFoxO靶标表达升高。TheBubR 1激酶死亡突变体有一个减少帽细胞的数量在女性生殖细胞，这可以通过表达组成型活性InR拯救。我们的结论是BubR 1激酶在果蝇中的一个主要生理作用是调节胰岛素信号。
As a core component of the mitotic checkpoint complex, BubR1 has a modular organization of molecular functions, with KEN box and other motifs at the N terminus inhibiting the anaphase-promoting complex/cyclosome, and a kinase domain at the C terminus, whose function remains unsettled, especially at organismal levels. We generate knock-inBubR1mutations in theDrosophilagenome to separately disrupt the KEN box and the kinase domain. All of the mutants are homozygously viable and fertile and show no defects in mitotic progression. The mutants without kinase activity have an increased lifespan and phenotypic changes associated with attenuated insulin signaling, including reduced InR on the cell membrane, weakened PI3K and AKT activity, and elevated expression of dFoxO targets. TheBubR1kinase-dead mutants have a reduced cap cell number in female germaria, which can be rescued by expressing a constitutively active InR. We conclude that one major physiological role of BubR1 kinase inDrosophilais to modulate insulin signaling.