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

DOI PDF Web Site 1 Citations 63 References Open Access

Abstract

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

Journal

  • Nature Communications

    Nature Communications 10 (1), 273-, 2019-01-17

    Springer Science and Business Media LLC

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