LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores

LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores
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LUBAC 通过将 CENP-E 靶向附着的动粒来控制染色体排列

DOI:
10.1038/s41467-018-08043-7
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发表时间:
2019-01
期刊:
Nature communication
影响因子:
--
通讯作者:
Huiyan Li
Huiyan Li
中科院分区:
其他
文献类型:
--
作者:
Min WU;Yan Chang;Huaibin Hu;Rui Mu;Yucheng Zhang;Xuanhe Qin;Xiaotao Duan;Weina Zhang;Weihua Li;Xuemin Zhang;Huiyan Li

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忠实的染色体分离要求在中期前期有适当的染色体聚集和中期染色体排列的动态维持。染色体错误分离会导致非整倍体、出生缺陷和癌症。着丝点结合的KMN网络和运动蛋白CENP-E对于着丝点微管附着和染色体稳定性至关重要。线性泛素链组装复合物(LUBAC)将线性泛素链连接到底物上,在免疫应答中具有良好的作用。在这里,我们确定LUBAC是有丝分裂期间染色体排列的关键参与者。LUBAC催化着丝点马达CENP-E的线性泛素化,这是CENP-E在附着着丝点定位而非非附着着丝点定位所特别需要的。KNL1作为线性泛素链的受体,在前期和中期将CENP-E锚定在附着的着丝点上。因此,线性泛素化通过将动态着丝点微管受体CENP-E与静态的KMN网络偶联来促进染色体聚集和动态染色体排列。
Faithful chromosome segregation requires proper chromosome congression at prometaphase and dynamic maintenance of the aligned chromosomes at metaphase. Chromosome missegregation can result in aneuploidy, birth defects and cancer. The kinetochore-bound KMN network and the kinesin motor CENP-E are critical for kinetochore-microtubule attachment and chromosome stability. The linear ubiquitin chain assembly complex (LUBAC) attaches linear ubiquitin chains to substrates, with well-established roles in immune response. Here, we identify LUBAC as a key player of chromosome alignment during mitosis. LUBAC catalyzes linear ubiquitination of the kinetochore motor CENP-E, which is specifically required for the localization of CENP-E at attached kinetochores, but not unattached ones. KNL1 acts as a receptor of linear ubiquitin chains to anchor CENP-E at attached kinetochores in prometaphase and metaphase. Thus, linear ubiquitination promotes chromosome congression and dynamic chromosome alignment by coupling the dynamic kinetochore microtubule receptor CENP-E to the static one, the KMN network.
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