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Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase

  1. Author:
    Yu, Fazhi
    Jiang, Ya
    Lu, Lucy
    Cao, Mimi
    Qiao, Yulong
    Liu, Xing
    Liu, Dan
    Van Dyke, Terry
    Wang, Fangwei
    Yao, Xuebiao
    Guo, Jing
    Yang, Zhenye

  2. Author Address

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Innovat Ctr Cell Biol, Sch Life Sci,Key Lab Innate Immun & Chron Dis CAS, Hefei, Anhui, Peoples R China.NCI, Ctr Adv Preclin Res, Ctr Canc Res, Frederick, MD 21701 USA.Chinese Acad Sci, Anhui Key Lab Cellular Dynam & Chem Biol, Ctr Excellence Mol Cell Sci, Hefei, Anhui, Peoples R China.Zhejiang Univ, Life Sci Inst, Hangzhou, Zhejiang, Peoples R China.Zhejiang Univ, Innovat Ctr Cell Biol, Hangzhou, Zhejiang, Peoples R China.
    1. Year: 2017
    2. Date: JAN 10
  2. Journal: CELL DISCOVERY
  3. NATURE PUBLISHING GROUP,
    1. 3
  5. Type of Article: Article
  6. Article Number: 16049
  7. ISSN: 2056-5968
  1. Abstract:

    Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear. Here we show that knockout, inhibition or blockade of the nuclear entry of Aurora-A severely decreased the centromere localization of Aurora-B and the phosphorylation of histone H3 threonine 3 (H3T3-ph) mediated by the kinase Haspin in late G2 phase. We further reveal that nuclear-accumulated Aurora-A phosphorylates Haspin at multiple sites at its N-terminus and that this promotes H3T3-ph and the rapid recruitment to the centromere of the chromosomal passenger complex. In addition, Aurora-A facilitates the association of Aurora-B with their common substrates: Haspin and Plk1. Notably, these functions of Aurora-A are mostly independent of Plk1. Thus we demonstrate that, in late G2 and prophase, Aurora-A phosphorylates Haspin to trigger the Haspin-H3T3ph-Aurora-B positive feedback loop that supports the timely establishment of the chromosomal passenger complex and the mitotic checkpoint before spindle assembly.

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External Sources

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  2. DOI: 10.1038/celldisc.2016.49
  3. View record in Web of Science®
  4. WOS: 000414900900001

Library Notes

  1. Fiscal Year: FY2016-2017
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