The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans
The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans
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DOI：
10.1016/j.cub.2005.11.070
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发表时间：
2006-01
期刊：
影响因子：
9.2
通讯作者：
M. Shirayama;M. Soto;T. Ishidate;Soyoung Kim;Kuniaki Nakamura;Y. Bei;S. V. D. Heuvel;C. Mello
中科院分区：
文献类型：
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作者：
M. Shirayama;M. Soto;T. Ishidate;Soyoung Kim;Kuniaki Nakamura;Y. Bei;S. V. D. Heuvel;C. Mello
背景在胚胎发生初期，关键的发育调节因子（称为决定因子）被不对称地激活，以确定体轴和组织层。Inc.在线虫中，这一过程部分由CCCH型锌指蛋白的保守家族调节，该家族指定早期胚胎细胞的命运。这些和其他决定因素的不对称本地化在早期胚胎通过电机依赖的物理易位以及选择性proteolysis.ResultsWe调节在这里显示，CCCH型锌指蛋白OMA-1作为一个连接的信号，调节从卵子发生到胚胎发生的过渡。虽然OMA-1在减数分裂期间促进卵母细胞成熟，但在第一次细胞分裂期间需要破坏OMA-1以启动细胞命运决定子的ZIF-1依赖性蛋白水解。4个保守的蛋白激酶基因mbk-2/Dyrk、kin-19/CK 1 α、gsk-3和cdk-1/CDC 2的突变可使OMA-1蛋白稳定，其表型可被anoma-1功能丧失突变部分抑制。OMA-1蛋白水解还依赖于细胞周期蛋白B3和基于ZIF-1非依赖性CUL-2的E3泛素连接酶复合物，以及CUL-2相互作用蛋白ZYG-11和Skp 1相关蛋白SKR-1和SKR-2。结论我们的研究结果表明，CDK 1/Cyclin B3依赖的活性将OMA-1蛋白水解与第一个细胞周期的完成联系起来，并支持OMA-1蛋白水解的模型。1的功能，以防止过早激活细胞命运的决定因素，直到他们在第一次有丝分裂不对称分配。
BackgroundAt the onset of embryogenesis, key developmental regulators called determinants are activated asymmetrically to specify the body axes and tissue layers. InC. elegans, this process is regulated in part by a conserved family of CCCH-type zinc finger proteins that specify the fates of early embryonic cells. The asymmetric localization of these and other determinants is regulated in early embryos through motor-dependent physical translocation as well as selective proteolysis.ResultsWe show here that the CCCH-type zinc finger protein OMA-1 serves as a nexus for signals that regulate the transition from oogenesis to embryogenesis. While OMA-1 promotes oocyte maturation during meiosis, destruction of OMA-1 is needed during the first cell division for the initiation of ZIF-1-dependent proteolysis of cell-fate determinants. Mutations in four conserved protein kinase genes—mbk-2/Dyrk,kin-19/CK1α,gsk-3, andcdk-1/CDC2—cause stabilization of OMA-1 protein, and their phenotypes are partially suppressed by anoma-1loss-of-function mutation. OMA-1 proteolysis also depends on Cyclin B3 and on a ZIF-1-independent CUL-2-based E3 ubiquitin ligase complex, as well as the CUL-2-interacting protein ZYG-11 and the Skp1-related proteins SKR-1 and SKR-2.ConclusionsOur findings suggest that a CDK1/Cyclin B3-dependent activity links OMA-1 proteolysis to completion of the first cell cycle and support a model in which OMA-1 functions to prevent the premature activation of cell-fate determinants until after they are asymmetrically partitioned during the first mitosis.