A role for cyclin E/Cdk2 in the timing of the midblastula transition in Xenopus embryos
A role for cyclin E/Cdk2 in the timing of the midblastula transition in Xenopus embryos
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DOI：
10.1006/dbio.1997.8647
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发表时间：
1997-08-15
影响因子：
2.7
通讯作者：
Maller, JL
中科院分区：
文献类型：
--
作者：
Hartley, RS;Sible, JC;Maller, JL
在非洲爪蟾的发育过程中，早期的细胞周期包括DNA合成和有丝分裂之间的快速振荡，直到完成第12次有丝分裂。然后周期延长并变为异步，合子转录开始，G期建立，这一时期被称为中囊胚过渡（MBT）。MBT的某些方面，如合子转录，依赖于阈值核与细胞质（N/C）比率的获得，而其他方面，如母体周期蛋白E的降解，与核事件无关，似乎由母体自主计时器控制。为了研究周期蛋白E在早期周期中的功能，在受精卵中，周期蛋白E/Cdk2激酶活性被截断形式的Xenopus Cdk抑制剂Xic1 （Delta 34Xic1）特异性抑制。Delta 34Xic1导致胚胎细胞周期延长，这与有丝分裂周期蛋白水平的增加有关。然而，DNA合成并未受到抑制。在注射Delta 34xic1的胚胎中，MBT的几个标志被延迟了几个小时，包括细胞周期蛋白E和A的消失，合子转录的开始，以及Cdc2上磷酸化酪氨酸的重新出现。在对照和注射Delta 34xic1的胚胎中，细胞周期蛋白E在第12次有丝分裂后随着合子转录的开始而降解，但α -amanitin的实验表明，细胞周期蛋白E的降解并不依赖于合子转录。因此，早期周期的长度和母体周期蛋白降解的时间取决于周期蛋白E/Cdk2活性。周期蛋白E/Cdk2活性在早期周期的振荡和周期蛋白E在MBT的消失都不依赖于蛋白质合成。这些数据表明，cyclin E/Cdk2与一个自主的母体计时器直接相关，该计时器驱动早期胚胎细胞周期直到MBT。(C) 1997学术出版社。
During Xenopus development, the early cell cycles consist of rapid oscillations between DNA synthesis and mitosis until completion of the 12th mitotic division. Then the cycle lengthens and becomes asynchronous, zygotic transcription begins, and G phases are established, a period known as the midblastula transition (MBT). Some aspects of the MBT, such as zygotic transcription, depend on acquisition of a threshold nuclear to cytoplasmic (N/C) ratio, whereas others, such as maternal cyclin E degradation, are independent of nuclear events and appear to be controlled by an autonomous maternal timer. To investigate the function of cyclin E during the early cycles, cyclin E/Cdk2 kinase activity was specifically inhibited in fertilized eggs by a truncated form of the Xenopus Cdk inhibitor, Xic1 (Delta 34Xic1). Delta 34Xic1 caused lengthening of the embryonic cell cycles that correlated with increased levels of mitotic cyclins. However, DNA synthesis was not inhibited. Several hallmarks of the MBT were delayed for several hours in Delta 34Xic1-injected embryos, including the disappearance of cyclins E and A, the initiation of zygotic transcription, and the reappearance of phosphotyrosine on Cdc2. In both control and Delta 34Xic1-injected embryos, cyclin E was degraded after the 12th mitotic division as zygotic transcription began, but experiments with alpha-amanitin show that cyclin E degradation is not dependent on zygotic transcription. Thus, the length of the early cycles and the timing of maternal cyclin degradation depend upon cyclin E/Cdk2 activity. Neither oscillations in cyclin E/Cdk2 activity during the early cycles nor the disappearance of cyclin E at the MBT were dependent on protein synthesis. These data suggest that cyclin E/Cdk2 is directly linked to an autonomous maternal timer that drives the early embryonic cell cycles until the MBT. (C) 1997 Academic Press.