Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules.Centromeres are captured by individual microtubules via a kinetochore constitutive centrome...Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules.Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network(CCAN)during chromosome segregation.CCAN contains 16 subunits,including CENP-W and CENP-T.However,the molecular recognition and mitotic regulation of the CCAN assembly remain elusive.Here,we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T.Aurora B phosphorylates CENP-W at threonine 60,which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis.These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.展开更多
目的探讨着丝粒蛋白W(centromere protein W,CENP-W)在人脑胶质瘤中的表达水平及与预后的相关性,并探讨其对脑胶质瘤细胞侵袭作用的影响。方法在高级别胶质瘤组织、低级别胶质瘤及瘤旁正常脑组织中,采用蛋白质印迹法、实时荧光定量PCR...目的探讨着丝粒蛋白W(centromere protein W,CENP-W)在人脑胶质瘤中的表达水平及与预后的相关性,并探讨其对脑胶质瘤细胞侵袭作用的影响。方法在高级别胶质瘤组织、低级别胶质瘤及瘤旁正常脑组织中,采用蛋白质印迹法、实时荧光定量PCR法检测CENP-W的表达水平,并统计分析表达水平与胶质瘤临床病理特征及预后的相关性,应用特异性siRNA干扰U251细胞中CENP-W表达使其下调后,通过Transwell侵袭实验观察转染CENPW siRNA对U251细胞侵袭能力的影响。结果胶质瘤组织CENP-W表达水平明显高于正常脑组织,并且与胶质瘤的病理级别呈正相关性;转染成功后,与空白对照组及阴性对照组比较,转染CENP-W-siRNA组的细胞侵袭及迁移能力均下降,Kaplan-Meier生存分析及Log-rank检验显示低表达CENP-W患者的PFS明显长于高表达组。结论CENP-W表达与胶质瘤的病理级别呈正相关,CENP-W可以促进脑胶质瘤的侵袭,预示CENP-W可作为胶质瘤治疗新靶点。展开更多
基金supported by the National Key Research and Development Program of China(2022YFA1303100,2022YFA0806800,2022YFA1302700,and 2017YFA0503600)the National Natural Science Foundation of China(32090040,92254302,92153302,92253301,22137007,32170733,and 31871359)+3 种基金the Ministry of Education(IRT_17R102)the Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000)the Fundamental Research Funds for the Central Universities(WK2070000066 and WK2070000194).
文摘Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules.Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network(CCAN)during chromosome segregation.CCAN contains 16 subunits,including CENP-W and CENP-T.However,the molecular recognition and mitotic regulation of the CCAN assembly remain elusive.Here,we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T.Aurora B phosphorylates CENP-W at threonine 60,which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis.These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.
文摘目的探讨着丝粒蛋白W(centromere protein W,CENP-W)在人脑胶质瘤中的表达水平及与预后的相关性,并探讨其对脑胶质瘤细胞侵袭作用的影响。方法在高级别胶质瘤组织、低级别胶质瘤及瘤旁正常脑组织中,采用蛋白质印迹法、实时荧光定量PCR法检测CENP-W的表达水平,并统计分析表达水平与胶质瘤临床病理特征及预后的相关性,应用特异性siRNA干扰U251细胞中CENP-W表达使其下调后,通过Transwell侵袭实验观察转染CENPW siRNA对U251细胞侵袭能力的影响。结果胶质瘤组织CENP-W表达水平明显高于正常脑组织,并且与胶质瘤的病理级别呈正相关性;转染成功后,与空白对照组及阴性对照组比较,转染CENP-W-siRNA组的细胞侵袭及迁移能力均下降,Kaplan-Meier生存分析及Log-rank检验显示低表达CENP-W患者的PFS明显长于高表达组。结论CENP-W表达与胶质瘤的病理级别呈正相关,CENP-W可以促进脑胶质瘤的侵袭,预示CENP-W可作为胶质瘤治疗新靶点。
