Ubiquitylation-dependent localization of PLK1 in mitosis

Jochen Beck, Sarah Maerki, Markus Posch, Thibaud Metzger, Avinash Persaud, Hartmut Scheel, Kay Hofmann, Daniela Rotin, Patrick Pedrioli, Jason R. Swedlow, Matthias Peter, Izabela Sumara

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    65 Citations (Scopus)

    Abstract

    Polo-like kinase 1 (PLK1) critically regulates mitosis through its dynamic localization to kinetochores, centrosomes and the midzone. The polo-box domain (PBD) and activity of PLK1 mediate its recruitment to mitotic structures, but the mechanisms regulating PLK1 dynamics remain poorly understood. Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and PLK1 kinetochore localization but not PLK1 stability. In the absence of KLHL22, PLK1 accumulates on kinetochores, resulting in activation of the spindle assembly checkpoint (SAC). CUL3-KLHL22 ubiquitylates Lys 492, located within the PBD, leading to PLK1 dissociation from kinetochore phosphoreceptors. Expression of a non-ubiquitylatable PLK1-K492R mutant phenocopies inactivation of CUL3-KLHL22. KLHL22 associates with the mitotic spindle and its interaction with PLK1 increases on chromosome bi-orientation. Our data suggest that CUL3-KLHL22-mediated ubiquitylation signals degradation-independent removal of PLK1 from kinetochores and SAC satisfaction, which are required for faithful mitosis.

    Original languageEnglish
    Pages (from-to)430-439
    Number of pages10
    JournalNature Cell Biology
    Volume15
    Issue number4
    DOIs
    Publication statusPublished - 2013

    Keywords

    • ROLES
    • COMPLEX
    • CELL-DIVISION
    • RING UBIQUITIN LIGASES
    • SPINDLE-ASSEMBLY CHECKPOINT
    • KINASE-1
    • E3 LIGASE
    • AURORA-B
    • POLO-BOX DOMAIN
    • POLO-LIKE-KINASE-1

    Cite this

    Beck, J., Maerki, S., Posch, M., Metzger, T., Persaud, A., Scheel, H., Hofmann, K., Rotin, D., Pedrioli, P., Swedlow, J. R., Peter, M., & Sumara, I. (2013). Ubiquitylation-dependent localization of PLK1 in mitosis. Nature Cell Biology, 15(4), 430-439. https://doi.org/10.1038/ncb2695