Wee1 kinase alters cyclin E/Cdk2 and promotes apoptosis during the early embryonic development of Xenopus laevis.
Wee1 kinase alters cyclin E/Cdk2 and promotes apoptosis during the early embryonic development of Xenopus laevis.
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WEE1激酶会改变细胞周期蛋白E/CDK2，并在Xenopus laevis的早期胚胎发育期间促进细胞凋亡。
DOI：
10.1186/1471-213x-7-119
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发表时间：
2007-10-25
影响因子：
--
通讯作者：
Sible JC
中科院分区：
文献类型：
--
作者：
Wroble BN;Finkielstein CV;Sible JC
非洲爪蟾胚胎的细胞周期从早期发育的中囊胚过渡（MBT）开始经历广泛的重塑。细胞分裂2-12由快速分裂组成，没有间隙期或细胞周期检查点。一些重塑事件依赖于关键的核质比，而另一些则依赖于由细胞周期蛋白E/Cdk2活性控制的母体计时器。在MBT中发生的一个关键事件是母体Wee1的降解，Wee1是细胞周期蛋白依赖性激酶（Cdk）活性的负调节因子。为了评估Wee1对胚胎细胞周期重塑的影响，将Wee1 mRNA注射到单细胞期胚胎中。在MBT之前，Wee1的过表达导致细胞周期延迟和Cdks的酪氨酸磷酸化。此外，Wee1的过表达破坏了通常发生在MBT上的关键发育事件，如Cdc25A、cyclin E和Wee1的降解。过表达Wee1也会导致mbt后细胞凋亡、Cdks酪氨酸磷酸化和细胞周期蛋白E/Cdk2活性的持续。为了确定胚胎的存活是否需要Cdk2，我们将周期蛋白E/Cdk2抑制剂Δ34-Xic1注射到胚胎中，结果显示其也能诱导细胞凋亡。综上所述，这些数据表明Wee1通过破坏细胞周期蛋白E/Cdk2定时器触发细胞凋亡。与Wee1和Δ34-Xic1相反，通过表达Chk1和Chk2激酶改变Cdks阻断而不是促进细胞凋亡，导致Cdc25A过早降解。总之，这些数据表明Cdc25A在X. laevis胚胎的凋亡发育调控程序中起关键作用。
The cell cycles of the Xenopus laevis embryo undergo extensive remodeling beginning at the midblastula transition (MBT) of early development. Cell divisions 2–12 consist of rapid cleavages without gap phases or cell cycle checkpoints. Some remodeling events depend upon a critical nucleo-cytoplasmic ratio, whereas others rely on a maternal timer controlled by cyclin E/Cdk2 activity. One key event that occurs at the MBT is the degradation of maternal Wee1, a negative regulator of cyclin-dependent kinase (Cdk) activity. In order to assess the effect of Wee1 on embryonic cell cycle remodeling, Wee1 mRNA was injected into one-cell stage embryos. Overexpression of Wee1 caused cell cycle delay and tyrosine phosphorylation of Cdks prior to the MBT. Furthermore, overexpression of Wee1 disrupted key developmental events that normally occur at the MBT such as the degradation of Cdc25A, cyclin E, and Wee1. Overexpression of Wee1 also resulted in post-MBT apoptosis, tyrosine phosphorylation of Cdks and persistence of cyclin E/Cdk2 activity. To determine whether Cdk2 was required specifically for the survival of the embryo, the cyclin E/Cdk2 inhibitor, Δ34-Xic1, was injected in embryos and also shown to induce apoptosis. Taken together, these data suggest that Wee1 triggers apoptosis through the disruption of the cyclin E/Cdk2 timer. In contrast to Wee1 and Δ34-Xic1, altering Cdks by expression of Chk1 and Chk2 kinases blocks rather than promotes apoptosis and causes premature degradation of Cdc25A. Collectively, these data implicate Cdc25A as a key player in the developmentally regulated program of apoptosis in X. laevis embryos.