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

First Author  Wu M Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  273
PubMed ID  30655516 Mgi Jnum  J:270249
Mgi Id  MGI:6277194 Doi  10.1038/s41467-018-08043-7
Citation  Wu M, et al. (2019) LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores. Nat Commun 10(1):273
abstractText  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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