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Molecular Mechanisms of Stopping and Starting the Cell Cycle

停止和启动细胞周期的分子机制

基本信息

批准号：
07408022
负责人：
KISHIMOTO Takeo
金额：
$ 15.94万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Meiotic cell cycle in oocytes is characterized by the arrest and release at G2-phase of immature oocytes, lack of S-phase in interkinesis period and the second arrest after the completion of meiosis. To elucidate the molecular mechanisms underlying these characteristics, we have found the followings in the project.1. G2-phase arrest and its release : G2-phase arrest in immature starfish oocytes is supported by Weel-like kinase, but not Weel itself. At the release, both phosphorylation of Cdc25 phosphatase and suppression of Weel-like kinase occur independently of cdc2 kinase activity, resulting in the initial activation of cdc2 kinase.2. Lack of S-phase in interkinesis period : We have developed from Xenopus oocyte extracts a cell-free system, "meiotic extracts", which mimics meiotic M/M transition. Successful N/N transition depends on both Mos, whose downstream is known MAP kinase and unknow pathway, and low protein levels of Weel.3. GI-phase arrest in mature eggs : In mature starfish eggs, MAP kinase activity is necessary and sufficient for the G1-phase arrest and suppression of S-phase. As an upstream of MAP kinase, we have isolated starfish Mos for the first time in invertebrate oocytes which do not arrest at the second meiotic metaphase. Comparison among Xenopus, mouse and starfish oocytes reveals that a conserved role of Mos might be to ensure the successful entry into meiosis II, thus preventing parthenogenetic activation.

卵母细胞减数分裂周期的特点是未成熟卵母细胞在G2期停滞和释放，间期缺少S期，减数分裂完成后出现第二次停滞。为了阐明这些特征背后的分子机制，我们在该项目中发现了以下几点。G2期停滞及其释放：未成熟海星卵母细胞的G2期停滞是由Weel样激酶支持的，而不是Weel本身。在释放时，CDC25磷酸酶的磷酸化和Weel样激酶的抑制都不依赖于cdc2激酶的活性，导致cdc2激酶的初始激活。在减数分裂间期缺乏S相：我们从非洲爪哇卵母细胞提取液中发展出一种无细胞系统，即“减数分裂提取液”，它模拟减数分裂M/M转变。成功的N/N转换依赖于下游为MAP激酶和未知途径的MOS和低水平的Weel2。成熟卵的Gi期停滞：在成熟的海星卵中，MAPK活性是G1期停滞和抑制S期的必要条件和充分条件。作为MAP激酶的上游，我们首次在无脊椎动物卵母细胞中分离到海星MOS，这些无脊椎动物卵母细胞在第二次减数分裂中期不会停止。对非洲爪哇、小鼠和海星卵母细胞的比较表明，MOS的保守作用可能是确保成功进入减数分裂II，从而阻止孤雌生殖激活。