Murakami M S, Copeland T D, Vande Woude G F
Advanced Bioscience Laboratories (ABL)-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 USA.
Genes Dev. 1999 Mar 1;13(5):620-31. doi: 10.1101/gad.13.5.620.
Several key developmental events occur in the first mitotic cell cycle of Xenopus; consequently this cycle has two gap phases and is approximately 60-75 min in length. In contrast, embryonic cycles 2-12 consist only of S and M phases and are 30 min in length. Xe-Wee1 and Mos are translated and degraded in a developmentally regulated manner. Significantly, both proteins are present in the first cell cycle. We showed previously that the expression of nondegradable Mos, during early interphase, delays the onset of M phase in the early embryonic cell cycles. Here we report that Xe-Wee1 is required for the Mos-mediated M-phase delay. We find that Xe-Wee1 tyrosine autophosphorylation positively regulates Xe-Wee1 and is only detected in the first 30 min of the first cell cycle. The level and duration of Xe-Wee1 tyrosine phosphorylation is elevated significantly when the first cell cycle is elongated with nondegradable Mos. Importantly, we show that the tyrosine phosphorylation of Xe-Wee1 is required for the Mos-mediated M-phase delay. These findings indicate that Mos positively regulates Xe-Wee1 to generate the G2 phase in the first cell cycle and establish a direct link between the MAPK signal transduction pathway and Wee1 in vertebrates.
非洲爪蟾的第一次有丝分裂细胞周期中会发生几个关键的发育事件；因此，这个周期有两个间隙期，长度约为60 - 75分钟。相比之下，胚胎周期2 - 12仅由S期和M期组成，长度为30分钟。非洲爪蟾Wee1（Xe - Wee1）和Mos以发育调控的方式进行翻译和降解。值得注意的是，这两种蛋白质在第一个细胞周期中都存在。我们之前表明，在早期间期表达不可降解的Mos会延迟早期胚胎细胞周期中M期的开始。在此我们报告，Xe - Wee1是Mos介导的M期延迟所必需的。我们发现Xe - Wee1酪氨酸自磷酸化正向调节Xe - Wee1，并且仅在第一个细胞周期的前30分钟被检测到。当第一个细胞周期因不可降解的Mos而延长时，Xe - Wee1酪氨酸磷酸化的水平和持续时间会显著升高。重要的是，我们表明Xe - Wee1的酪氨酸磷酸化是Mos介导的M期延迟所必需的。这些发现表明，Mos正向调节Xe - Wee1以在第一个细胞周期中产生G2期，并在脊椎动物中建立了丝裂原活化蛋白激酶（MAPK）信号转导通路与Wee1之间的直接联系。
