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蛋白质磷酸化修饰及其在细胞周期调控中的作用研究进展

谭锬 柯柏怡 梁前进

谭锬, 柯柏怡, 梁前进. 蛋白质磷酸化修饰及其在细胞周期调控中的作用研究进展[J]. 北京师范大学学报(自然科学版). doi: 10.12202/j.0476-0301.2023078
引用本文: 谭锬, 柯柏怡, 梁前进. 蛋白质磷酸化修饰及其在细胞周期调控中的作用研究进展[J]. 北京师范大学学报(自然科学版). doi: 10.12202/j.0476-0301.2023078
TAN Tan, KE Baiyi, LIANG Qianjin. Research Progress on Protein phosphorylation Modification and its Role in Regulating Cell Cycle Progression[J]. Journal of Beijing Normal University(Natural Science). doi: 10.12202/j.0476-0301.2023078
Citation: TAN Tan, KE Baiyi, LIANG Qianjin. Research Progress on Protein phosphorylation Modification and its Role in Regulating Cell Cycle Progression[J]. Journal of Beijing Normal University(Natural Science). doi: 10.12202/j.0476-0301.2023078

蛋白质磷酸化修饰及其在细胞周期调控中的作用研究进展

doi: 10.12202/j.0476-0301.2023078
基金项目: 湖南省自然科学基金资助项目(2020JJ5478),国家自然科学基金资助项目(31571394),北京师范大学教学建设与改革/信息化与教育教学融合项目基金资助项目(18-04-05)
详细信息
    通讯作者:

    梁前进,教授,博士生导师。研究方向:细胞遗传学. E-mail: Lqj@bnu.edu.cn

  • 中图分类号: Q2

Research Progress on Protein phosphorylation Modification and its Role in Regulating Cell Cycle Progression

  • 摘要: 细胞周期是真核生物实现细胞分裂与增殖、从母代向子代传递遗传信息的连续过程.真核细胞通过蛋白质水平的周期性调控完成细胞的分裂与增殖,细胞周期的紊乱常与肿瘤等疾病密切相关.蛋白质磷酸化修饰是细胞周期进程中一种主要的调控方式,可以改变蛋白质的分子结构,影响其与其他分子间的相互作用,从而调节相关分子的生物学活性及功能.细胞周期相关蛋白的磷酸化与非磷酸化状态的改变犹如“分子开关”,精细地控制着周期进程和细胞分裂系列事件.周期相关蛋白质的多位点磷酸化机制研究是磷酸化研究的一个热点.本文综合评述细胞周期调控进程中部分重要蛋白的磷酸化修饰机制,总结了近年来细胞周期领域中蛋白质磷酸化修饰方面的新发现、新突破,为进一步深入理解蛋白质磷酸化及细胞周期调控机制提供参考.

     

  • 图  1  过程式磷酸化蛋白和超位移磷酸化蛋白在Phos-tag™ SDS-PAGE中泳动情况的模式

    a. 发生过程式磷酸化的蛋白因分子间磷酸化程度不均一,常在Phos-tag™ SDS-PAGE表现为多条磷酸化蛋白条带;b. 发生超位移磷酸化蛋白因各个分子均磷酸化程度较高,在短时间内所有蛋白分子磷酸化程度呈现均一性,常在Phos-tag™ SDS-PAGE中表现出单一条带.这里的Phos-tag™(也称Phosbind)是在中性pH条件下(生理pH)能特异性结合磷酸离子的一种功能性双环金属络合物.Phos-tag™ Acrylamide可用于磷蛋白的电泳分离,Phos-tag™ Biotin可用于磷蛋白的Western blot检测,Phos-tag™ Agarose可用于磷蛋白纯化,Phos-tag™ Mass分析试剂盒可用于磷蛋白质谱(MALDI-TOF/MS)检测.由于Phos-tag捕获磷酸基团的专门特性,Phos-tag磷酸亲和分析法获得的蛋白磷酸化分析结果可靠性强,代表了蛋白质磷酸化研究的一项技术发展.

    图  2  蛋白质磷酸化示意

    a. 单一或少数位点蛋白质底物(S)磷酸化由专一性激酶催化,在Mg2+的参与下,将ATP上的γ位磷酸基团(P)转移到蛋白质的丝氨酸、苏氨酸或者酪氨酸等氨基酸残基上;专一性磷酸酶则负责对磷蛋白进行去磷酸化,某些磷酸酶的活化也可能需要其他金属离子,如Ca2+的参与.b. 多位点蛋白质底物磷酸化除了需要ATP、Mg2+的参与,常需要其他非激酶蛋白的参与,例如Cdk/Cyclin介导的多位点磷酸化,需要Cks蛋白的辅助参与;超位移磷酸化也可能需要其他非激酶蛋白(因子)的参与.

    表  1  部分M期发生超位移磷酸化的人类蛋白

    蛋白名称间期功能M期功能参考文献
    Bora核仁组织中心成员激活AURKA和Plk1[52]
    NUP35核孔组成蛋白调控纺锤体组装和染色体定位[53]
    NUP98核孔组成蛋白调控纺锤体极性[54]
    TPR核孔组成蛋白调控纺锤体检验点[55]
    CENPF核基质组成蛋白M期着丝粒组成蛋白[56]
    CENPT核体组成蛋白M期着丝粒组成蛋白[57]
    INCENP核质和核体的组成蛋白染色体过客复合物组成蛋白[58]
    Ki-67核质和核仁的组成蛋白包裹染色体的周围区域[59]
    NuMA1核基质组成蛋白与有丝分裂纺锤极基质相关[60]
    YAP1转录激活调控纺锤体检验点[61]
    53BP1DNA损伤应答动粒有丝分裂检查点信号[62]
    BRCA1DNA损伤应答调控纺锤体组装[63]
    Paxillin黏着斑组成蛋白促进双极性纺锤体形成[64]
    Zyxin黏着斑组成蛋白与有丝分裂器有关[65]
    Anillin核内actin结合蛋白调控胞质分裂[66]
    MAP7稳定微管控制纺锤体长度[67]
    BCL9Wnt信号通路成员调控纺锤体组装[68]
    MINK1信号通路激酶调控胞质分裂[69]
    STIM1调控内质网结构和功能阻隔内质网与纺锤体的结合[70]
    Dynactin 1Dynein驱动的囊泡运输纺锤体定向[71]
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  • 收稿日期:  2023-05-04
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