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| 1 | BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association to end-on capture of spindle microtubules显示文摘Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, powered congression of those chromosomes, their segregation in anaphase, and assembly of a spindle midzone at mitotic exit. The centromere-associated kinesin motor CENP-E, whose binding partner is BubR1, has been implicated in congression of misaligned chromosomes and the transition from lateral kinetochore-microtubule association to end-on capture. Although previously proposed to be a pseudokinase, here we report the structure of the kinase domain of Drosophila melanogaster BubR1, revealing its folding into a conformation predicted to be catalytically active. BubR1 is shown to be a bona fide kinase whose phosphorylation of CENP-E switches it from a laterally attached microtubule motor to a plus-end microtubule tip tracker. Computational modeling is used to identify bubristatin as a selective BubR1 kinase antagonist that targets the αN1 helix of N-terminal extension and αC helix of the BubR1 kinase domain. Inhibition of CENP-E phosphorylation is shown to prevent proper microtubule capture at kinetochores and, surprisingly, proper assembly of the central spindle at mitotic exit. Thus, BubR1-mediated CENP-E phosphorylation produces a temporal switch that enables transition from lateral to end-on microtubule capture and organization of microtubules into stable midzone arrays. | Yuejia Huang Lin Lin Xing Liu Sheng Ye Phil Y. Yao Wenwen Wang Fengrui Yang Xinjiao Gao Junying Li Yin Zhang Jiancun Zhang Zhihong Yang Xu Liu Zhenye Yang Jianye Zang Maikun Teng Zhiyong Wang Ke Ruan Xia Ding Lin Li Don W. Cleveland Rongguang Zhang Xuebiao Yao | 2019 | Cell Research2019，29，7： | 8 |
| 2 | Mitosis-specific acetylation tunes Ran effector binding for chromosome segregation显示文摘在房间期间,分割要求忠诚有丝分裂的锭子汇编和染色体分离的基因信息的稳定的传播。运用了 GTPase 戏在有丝分裂的锭子汇编的一个关键角色。然而,在锭子的 Ran-GTP 的一个化学坡度的产生怎么被联合到有丝分裂的 translational 以后修正,从来没被描绘过。这里,我们解决了复杂结构与核苷酸版本因素 Mog1 跑了并且描出一个新奇有丝分裂特定的调整 acetylation 的 Ran-Mog1 相互作用在染色体分离期间。我们的指导结构的功能的分析表明那 Mog1 与 RCC1 竞争为以一种 GTP/GDP-dependent 方式变有约束力。生物化学的描述表明了那 Mog1 固定跑阻止 RCC1 有约束力、随后的 GTP 装载。令人惊讶地,跑了是 TIP60 的真正的底层,并且由 TIP60 的 Lys134 的 acetylation 解放 Mog1 从在有丝分裂期间变有约束力。重要地,这个得到 acetylation 的开关对 RCC1 变有约束力支持 Ran-GTP 的高水平,它为染色体排列是必要的。这些结果建立一以前 TIP60 由调节在提供 Ran-GTP 水平的 homeostatic 控制的规章的机制运用了的 uncharacterized 为在有丝分裂的染色体分离的受动器绑定。 | Xiaoling Bao Heng Liu Xing Liu Ke Ruan Yonshui Zhang Zhiyong Zhang Qi Hu Ying Liu Saima Akram Jiahai Zhang Qingguo Gong Wenwen wang Xiao Yuan Jian-Li Lingli Zhao Zhen Dou Ruijun Tian Xuebiao Yao Jihui Wu Yunyu Shi | 2018 | Journal of Molecular Cell Biology2018，10，1： | 8 |
| 3 | Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly显示文摘Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive.Given the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids.Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during mitosis.Highresolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype.Using biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic cells.Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone.Thus,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays.These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly.Since CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis. | Xu Liu Leilei Xu Junying Li Phil Y.Yao Wanjuan Wang Hazrat Ismail Haowei Wang Bryce Liao Zhihong Yang Tarsha Ward Ke Ruan Jianchun Zhang Quan Wu Ping He Xia Ding Dongmei Wang Chuanhai Fu Zhen Dou Feng Yan Wenwen Wang Xing Liu Xuebiao Yao | 2020 | Journal of Molecular Cell Biology2020，12，8： | 3 |
| 4 | 细胞有丝分裂马达蛋白的化学生物学研究与展望显示文摘微管马达驱动蛋白(kinesin,简称驱动蛋白)是一类沿着微管的特定方向行走的分子马达蛋白家族,在胞内运输和细胞分裂中扮演着重要角色.为了研究驱动蛋白的时空动力学特征,过去近15年的化学生物学研究发掘了一系列特异性的小分子抑制剂,为解析驱动蛋白的系统功能提供了有效的工具.由于部分驱动蛋白在实体瘤中活性异常增高,驱动蛋白小分子抑制剂渐渐发展成为癌症化疗的先导化合物.事实上,基于驱动蛋白Eg5(也叫KIF11)和CENP-E(着丝粒结合蛋白E)的小分子抑制剂已经进入Ⅰ期和Ⅱ期临床实验.本文将简介驱动蛋白的小分子抑制剂研究进展及临床转化研究前景. | 刘行 姚雪彪 | 2014 | 科学通报2014，59，31： | 1 |
| 5 | 基于生物信息学分析CENPE在肺腺癌中的表达及临床意义显示文摘目的探讨着丝粒蛋白E(CENPE)在肺腺癌中的表达及临床意义。方法通过TCGA和GEO数据库获得CENPE在肺腺癌中的表达数据及相关临床特征参数,比较CENPE在肺腺癌组织和正常组织中的表达差异;分析CENPE表达与肺腺癌患者临床特征、驱动基因突变、免疫治疗靶点及预后的关系;通过构建列线图模型进一步探讨联合CENPE及相关临床参数在预后监测中的作用;采用基因富集分析(GSEA)探讨CENPE相关的信号通路。最后,在TIMER数据库中观察CENPE在泛肿瘤组织中的表达与临床意义。结果在TCGA、GSE31210、GSE10072、GSE32863、GSE40791和GSE75037等数据库中,CENPE表达水平在肺腺癌组织中高于正常组织(均P<0.001)。HPA数据库的免疫组化结果提示,CENPE蛋白在肺腺癌组织中呈高表达。CENPE的表达与年龄、性别、吸烟史、T分期、N分期、TNM分期、EGFR/KRAS突变状态及PD-L1的表达等密切相关(均P<0.05)。CENPE高表达组患者总体生存率低于低表达组(P<0.05),且可以作为肺腺癌患者的独立预后因子。基于T分期、N分期及CENPE表达的列线图模型,能更准确地预测肺腺癌患者的预后。GSEA结果提示,CENPE高表达患者在有丝分裂纺锤体、mTOR信号通路、G2M检查点、Myc信号通路、E2F靶点、未折叠蛋白反应及DNA损伤修复等信号通路集中。在TIMER数据库中观察到,CENPE在泛肿瘤组织中高表达,并与患者的恶性生物学表型相关。结论CENPE在肺腺癌患者中呈高表达,与患者的恶性表型及不良预后相关,可作为治疗筛选及预后监测的潜在生物标志物。 | 李群荣 胡艳 曹娟 王大伟 范浩 胡旭钢 | 2021 | 浙江临床医学2021，23，9： | 0 |
| 6 | Organoid-based chemical approach to dissect the mechanism controlling cellular dynamics显示文摘Organoids are self-organizing in vitrothree-dimensional(3D)tissue culturescontaining multiple types of cells.Com-pared to traditional two-dimensional(2D)cell culture systems,3D organoids bet-ter replicate the architecture,complex-ity,and physiology of an organ(Figure1).ln addition,3D organoids are eas-ier to scale up and more cost-efficientwhen compared to animal models. | Lauretta A.Lacko Shuibing Chen | 2020 | Journal of Molecular Cell Biology2020，12，8： | 0 |
| 7 | 纺锤体可塑性与动力学调控显示文摘细胞精确的自我复制依赖纺锤体的可塑性和精准调控。功能纺锤体的形成取决于着丝粒动力学、纺锤体微管和星状微管可塑性的时空动态调控。纺锤体的可塑性研究在过去的三十年间取得了迅猛的发展,生物化学研究发现并鉴定了大量的纺锤体蛋白与翻译后修饰,结构生物学研究解析和阐明了部分关键蛋白的结构和作用机制。如何解析纺锤体高级结构的变化与其对应的生物学意义,并把纺锤体的动态表观标示转化为三维类器官干细胞增殖的质量控制标准将是下一阶段纺锤体可塑性与调控研究的重要科学问题。该文将简介纺锤体可塑性与动力学研究进展及研究前景。 | 刘行 刘旭 姚雪彪 | 2019 | 中国细胞生物学学报2019，41，3： | 0 |
| 8 | Article Navigation Syntelin inhibits triple-negative breast cancer cell proliferation and metastasis显示文摘Dear Editor,The hallmarks of cancer comprise several distinct biological characteristics acquired during the multistep development of human tumors with the unique feature of genomic instability(Shen,2011).These cancer characteristics include sustaining proliferative signaling,evading growth suppressors,resisting cell death,enabling replicative immortality,inducing angiogenesis,and activating invasion and metastasis(Chen et al.,2011;Song et al.,2018).Triple-negative breast cancer(TNBC),an aggressive disease with increased risks for visceral metastases,has a poor prognosis due to unavailable and viable therapeutic targets(Bianchini et al.,2016).A TNBC diagnosis indicates that cancer cells test negative for three key receptors:estrogen receptor,progesterone receptor,and human epidermal growth factor receptor 2(Bianchini et al.,2016).The absence of these three receptors renders existing hormone and targeted therapies ineffective. | McKay Mullen Fengrui Yang Jun Cao Yang Cao Xu Liu Gee Young Lee Tao Li William Yao Zhihong Yang Jiahai Zhang Kela Johnson Felix Aikhionbare Yong Chen Xinjiao Gao Dongmei Wang Xia Ding Hadiyah-Nicole Green Xing Liu Xuebiao Yao | 2021 | Journal of Molecular Cell Biology2021，13，11： | 0 |
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