Molecular Mechanisms of Stopping and Starting the Cell Cycle

停止和启动细胞周期的分子机制

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07408022/
• 关键词: cell cycle control; meiosis; fertilization; cdc2 kinase; Cdc25 phosphatase; Weel kinase; Mos; MAP kinase; 細胞周期; 減数分裂周期; G2; M; G1; S移行; 核外移出; Junキナーゼ; M期開始; S期抑制; cdc25フォスファターゼ; S期開始; cell cycle control; meiosis; fertilization; cdc2 kinase; Cdc25 phosphatase; Weel kinase; Mos; MAP kinase; 細胞周期; 減数分裂周期; G2; M; G1; S移行; 核外移出; Junキナーゼ; M期開始; S期抑制; cdc25フォスファターゼ; S期開始

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.

卵母细胞中的减数分裂细胞周期的特征是在未成熟卵母细胞的G2期停滞和释放，在互际时期缺乏S期，以及减数分裂完成后的第二次逮捕。为了阐明这些特征的分子机制，我们发现了项目中的以下内容。1。 G2相逮捕及其释放：未成熟的海星卵母细胞中的G2相滞留得到了象鼻状的激酶的支持，但不是自身。在释放中，Cdc25磷酸酶的磷酸化和象征样激酶的抑制都独立于Cdc2激酶活性，从而导致Cdc2激酶的初始激活。2。在互际时期缺乏S期：我们已经从爪蟾卵母细胞提取了无细胞的系统“减数分裂提取物”，该系统模拟了减数分裂M/M的过渡。成功的N/N转变取决于MOS的MOS，其下游是已知的MAP激酶和未知的途径，以及低蛋白质水平3。 Gi-phase在成熟卵中停滞：在成熟的海星卵中，MAP激酶活性对于G1期停滞和S相抑制是必要的，足以满足。作为MAP激酶的上游，我们在无脊椎动物卵母细胞中首次有孤立的海星MOS，这些卵母细胞在第二次减数分裂中期没有停滞。爪蟾，小鼠和海星卵母细胞之间的比较表明，MOS的保守作用可能是确保成功地进入减数分裂II，从而防止遗传激活。