IDENTIFICATION OF A DEVELOPMENTAL TIMER REGULATING THE STABILITY OF EMBRYONIC CYCLIN-A AND A NEW SOMATIC A-TYPE CYCLIN AT GASTRULATION
IDENTIFICATION OF A DEVELOPMENTAL TIMER REGULATING THE STABILITY OF EMBRYONIC CYCLIN-A AND A NEW SOMATIC A-TYPE CYCLIN AT GASTRULATION
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DOI：
10.1101/gad.9.10.1164
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发表时间：
1995-05-15
影响因子：
10.5
通讯作者：
NEWPORT, JW
中科院分区：
文献类型：
--
作者：
HOWE, JA;HOWELL, M;NEWPORT, JW
我们已经确定了第二个非洲爪蟾细胞周期蛋白A，称为细胞周期蛋白A2。细胞周期蛋白A2是一个46.6 kD的蛋白质，与人类细胞周期蛋白A的同源性比先前鉴定的非洲爪蟾细胞周期蛋白A1更高。它存在于整个胚胎发育过程中（至少到46期），并且在成体组织以及非洲爪蟾组织培养细胞系中发现。相比之下，细胞周期蛋白A1存在于卵子和早期胚胎中，但不能在晚期胚胎或组织培养细胞中检测到。我们已经发现，编码这两种细胞周期蛋白A蛋白的mRNAs的母体凝视池在原肠胚形成开始之前是稳定的，然后突然降解。此时，新的转录取代细胞周期蛋白A2 mRNA。有趣的是，我们还观察到细胞周期蛋白A的稳定性在这个时候发生了巨大的变化。在原肠胚形成开始之前，细胞周期蛋白A1蛋白在细胞周期的间期是稳定的。然而，在原肠胚形成时，A1和A2蛋白在细胞周期的间期迅速翻转。总之，这些结果表明，控制细胞周期蛋白A蛋白和mRNA稳定性的发育程序在原肠胚形成时被激活。我们已经表明，这个程序是独立的新的转录开始在中期囊胚过渡。此外，用放线菌酮处理早期胚胎表明，这种降解程序的激活不依赖于细胞分裂和翻译。总的来说，我们的观察结果表明，以前未表征的定时机制激活新的降解途径在原肠胚形成的开始，这可能发挥重要作用，从母体编程释放细胞。
We have identified a second Xenopus cyclin A, called cyclin A2. Cyclin A2 is a 46.6-kD protein that shows a greater homology to human cyclin A than to the previously identified Xenopus cyclin A1. It is present throughout embryonic development (up to stage 46 at least) and is found in adult tissues as well as in Xenopus tissue culture cell lines. In contrast, cyclin A1 is present in eggs and early embryos but cannot be detected in late embryos or in tissue culture cells. We have found that the maternally stared pools of mRNAs encoding both of these cyclin A proteins are stable until the onset of gastrulation and then are degraded abruptly. At this time, new transcription replaces cyclin A2 mRNA. Interestingly, we have also observed a dramatic change in the stability of the cyclin A proteins at this time. Prior to the onset of gastrulation, cyclin A1 protein is stable during interphase of the cell cycle. At gastrulation, however, both A1 and A2 proteins turn over rapidly during interphase of the cell cycle. Together, these results indicate that developmental programs controlling cyclin A protein and mRNA stability are activated at gastrulation. We have shown that this program is independent of new transcription beginning at the mid-blastula transition. furthermore, treatment of early stage embryos with cycloheximide demonstrates that activation of this degradative program is independent of cell division and translation. Collectively, our observations suggest that a previously uncharacterized timing mechanism activates new degradative pathways at the onset of gastrulation, which could play an essential role in releasing cells from maternal programming.