Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic cell cycle progression during Arabidopsis gametogenesis
Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic cell cycle progression during Arabidopsis gametogenesis
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RING 型 E3 连接酶对细胞周期蛋白依赖性激酶抑制剂 ICK4/KRP6 的靶向降解对于拟南芥配子发生过程中的有丝分裂细胞周期进程至关重要
DOI：
10.1105/tpc.108.059741
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发表时间：
2008-06-01
期刊：
影响因子：
11.6
通讯作者：
Qu, Li-Jia
中科院分区：
文献类型：
--
作者：
Liu, Jingjing;Zhang, Yiyue;Qu, Li-Jia
减数分裂后，植物配子体通过两轮或三轮有丝分裂发育。虽然拟南芥配子体发育的个体发育已经被确定，但调控有丝分裂细胞周期进程的分子机制还不是很清楚。在这里，我们报道了环-H2基团F1a(RHF1a)和RHF2a这两个环指E3连接酶在拟南芥配子发生中发挥重要作用。在花粉发育的小孢子阶段和胚囊发育的雌配子体阶段，由于有丝分裂细胞周期的间期停滞，双突变体在雄配子体和雌配子体的形成中存在缺陷。我们证明了RHF1a直接与细胞周期蛋白依赖的激酶抑制因子ICK4/KRP6(CDc2Kinase4/KIP相关蛋白6的相互作用)相互作用，并以此为靶点进行蛋白酶体介导的降解。两个冗余的RHF基因失活导致ICK4/KRP6的积累，ICK4/KRP6的表达降低在很大程度上挽救了双突变体的配子体缺陷，表明ICK4/KRP6是RHF E3连接酶的底物。有趣的是，原位杂交显示ICK4/KRP6在减数分裂过程中主要在孢子体中表达。我们的发现表明，RHF1a/2a介导的减数分裂积累的ICK4/KRP6的降解对于确保拟南芥随后的有丝分裂形成配子体的进程是必不可少的。
Following meiosis, plant gametophytes develop through two or three rounds of mitosis. Although the ontogeny of gametophyte development has been defined in Arabidopsis thaliana, the molecular mechanisms regulating mitotic cell cycle progression are not well understood. Here, we report that RING-H2 group F 1a (RHF1a) and RHF2a, two RING-finger E3 ligases, play an important role in Arabidopsis gametogenesis. The rhf1a rhf2a double mutants are defective in the formation of male and female gametophytes due to interphase arrest of the mitotic cell cycle at the microspore stage of pollen development and at female gametophyte stage 1 of embryo sac development. We demonstrate that RHF1a directly interacts with and targets a cyclin-dependent kinase inhibitor ICK4/KRP6 (for Interactors of Cdc2 Kinase 4/Kip-related protein 6) for proteasome-mediated degradation. Inactivation of the two redundant RHF genes leads to the accumulation of ICK4/KRP6, and reduction of ICK4/KRP6 expression largely rescues the gametophytic defects in rhf1a rhf2a double mutants, indicating that ICK4/KRP6 is a substrate of the RHF E3 ligases. Interestingly, in situ hybridization showed that ICK4/KRP6 was predominantly expressed in sporophytes during meiosis. Our findings indicate that RHF1a/2a-mediated degradation of the meiosis-accumulated ICK4/KRP6 is essential to ensure the progression of subsequent mitoses to form gametophytes in Arabidopsis.