"Molecular Characterization of the Additional Components of MPF Activity"

“MPF 活性其他成分的分子表征”

• 批准号: 9405699
• 负责人: Jian Kuang
• 金额: $ 20万
• 依托单位: University of Texas, M.D. Anderson Cancer Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9405699&HistoricalAwards=false
• 关键词: Molecular; Characterization; Additional; Components; MPF

9405699 Kuang One of the central problems in cell biology is the control mechanism regulating the initiation of mitosis and meiosis (M phase) during the cell cycle. Maturation promoting factor (MPF), which is an M phase-specific activity functionally defined by its ability to induce Xenopus oocyte maturation (meiotic division), is hypothesized to be the mitotic inducer in all eukaryotic cells. Although currently MPF activity is attributed solely to the p34cdc2 kinase/cyclin B complex, this proposal has provided evidence for the working hypothesis that MPF activity is due to an autocatalytic system consisting of p34cdc2/cyclin B, and at least three distinct proteins recognized by the anti-phosphoepitope antibody MPM-2, and the kinase(s) that phosphorylate these MPM-2 antigens. The three MPM-2 antigens with MPF activity include the identified activator of cdc2 kinase, cdc25, and two unidentified activators of cdc2 kinase, designated MPF-QE1 and MPF-QE2. The kinase(s) that phosphorylate these three MPM-2 antigens are in turn activated by p34cdc2/cyclin B. To examine this hypothesis, the proposed research is aimed at the purification and molecular cloning of MPF-QE1, MPF- QE2 and the kinase that phosphorylates the MPM-2 epitope on them. Availability of their cDNA clone will facilitate the generation of the purified proteins and antibodies against them. These reagents will allow the characterization of their respective contribution in the activation of cdc2 kinase and M-phase induction. It is likely that information generated from the molecular characterization of the additional components of MPF activity will significantly facilitate our understanding of the regulation of M-phase induction during the eukaryotic cell cycle. %%% This proposal concerns the study of the process called cell cycle, by which all cells proliferate. Cell proliferation under normal conditions gives rise to the multitude of cells that living organisms are composed of and allows for their growth and regeneration. Conversely, uncontrolled cell proliferation often results in disorders such as cancer. Thus the control of cell cycle is one of the most fundamental problems in biology. This proposal addresses the control of cell cycle, the molecular mechanism that regulates the initiation of mitosis. The driving hypothesis of the proposal is that MPF is a multicomponent system that plays the role of the "decision committee" for the initiation of mitosis. The ultimate goal of the proposal is to identify all important components of this process and to determine their interaction in the cell cycle process. ***

小行星9405699 细胞生物学中的中心问题之一是调节细胞周期中有丝分裂和减数分裂（M期）起始的控制机制。 成熟促进因子（Maturation promoting factor，MPF）是一种M期特异性活性物质，具有诱导非洲爪蟾卵母细胞成熟（减数分裂）的功能，被认为是所有真核细胞的有丝分裂诱导因子。 尽管目前MPF活性仅归因于p34 cdc 2激酶/细胞周期蛋白B复合物，但该提议为工作假设提供了证据，即MPF活性是由于由p34 cdc 2/细胞周期蛋白B和至少三种由抗磷酸化表位抗体MPM-2识别的不同蛋白质以及磷酸化这些MPM-2抗原的激酶组成的自催化系统。 具有MPF活性的三种MPM-2抗原包括鉴定的cdc 2激酶激活剂cdc 25和两种未鉴定的cdc 2激酶激活剂MPF-QE 1和MPF-QE 2。 磷酸化这三种MPM-2抗原的激酶又被p34 cdc 2/细胞周期蛋白B激活。 为了检验这一假设，所提出的研究旨在MPF-QE 1、MPF-QE 2和使其上的MPM-2表位磷酸化的激酶的纯化和分子克隆。 它们的cDNA克隆的可用性将促进纯化蛋白质和针对它们的抗体的产生。 这些试剂将允许表征它们各自在cdc 2激酶活化和M期诱导中的贡献。 这是可能的，从分子表征的MPF活性的其他组件产生的信息将显着促进我们的理解，在真核细胞周期的M期诱导的调节。 %该提案涉及对所有细胞增殖的细胞周期过程的研究。 正常条件下的细胞增殖产生了组成生物体的众多细胞，并允许它们生长和再生。 相反，不受控制的细胞增殖往往导致疾病，如癌症。 细胞周期调控是生物学中最基本的问题之一。 该提案涉及细胞周期的控制，即调节有丝分裂起始的分子机制。 该提案的驱动假设是，MPF是一个多组分系统，在有丝分裂的启动中扮演着“决策委员会”的角色。 该提案的最终目标是确定这一过程的所有重要组成部分，并确定它们在细胞周期过程中的相互作用。 ***