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The Bub1–Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation

Author

Listed:
  • Luying Jia

    (Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA)

  • Bing Li

    (Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA)

  • Hongtao Yu

    (Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA)

Abstract

The spindle checkpoint senses unattached kinetochores and inhibits the Cdc20-bound anaphase-promoting complex or cyclosome (APC/C), to delay anaphase, thereby preventing aneuploidy. A critical checkpoint inhibitor of APC/CCdc20 is the mitotic checkpoint complex (MCC). It is unclear whether MCC suffices to inhibit all cellular APC/C. Here we show that human checkpoint kinase Bub1 not only directly phosphorylates Cdc20, but also scaffolds Plk1-mediated phosphorylation of Cdc20. Phosphorylation of Cdc20 by Bub1–Plk1 inhibits APC/CCdc20 in vitro and is required for checkpoint signalling in human cells. Bub1–Plk1-dependent Cdc20 phosphorylation is regulated by upstream checkpoint signals and is dispensable for MCC assembly. A phospho-mimicking Cdc20 mutant restores nocodazole-induced mitotic arrest in cells depleted of Mad2 or BubR1. Thus, Bub1–Plk1-mediated phosphorylation of Cdc20 constitutes an APC/C-inhibitory mechanism that is parallel, but not redundant, to MCC formation. Both mechanisms are required to sustain mitotic arrest in response to spindle defects.

Suggested Citation

  • Luying Jia & Bing Li & Hongtao Yu, 2016. "The Bub1–Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10818
    DOI: 10.1038/ncomms10818
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    Cited by:

    1. Ho-Soo Lee & Sunwoo Min & Ye-Eun Jung & Sunyoung Chae & June Heo & Jae-Ho Lee & TaeSoo Kim & Ho-Chul Kang & Makoto Nakanish & Sun-Shin Cha & Hyeseong Cho, 2021. "Spatiotemporal coordination of the RSF1-PLK1-Aurora B cascade establishes mitotic signaling platforms," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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