title: Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase.
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-H3T3-ph-Aurora-B positive feedback loop that supports the timely establishment of the chromosomal passenger complex and the mitotic checkpoint before spindle assembly.
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Fazhi
authors.initials: F
authors.lastname: Yu
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Center for Advanced Preclinical Research, the Center for Cancer Research, National Cancer Institute , Frederick, MD, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Cao
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Anhui Key laboratory for Cellular Dynamics & Chemical Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science , Hefei, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Center for Advanced Preclinical Research, the Center for Cancer Research, National Cancer Institute , Frederick, MD, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Van Dyke
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University , Hangzhou, China.
authors.forename: Fangwei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Anhui Key laboratory for Cellular Dynamics & Chemical Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science , Hefei, China.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Innate Immunity and Chronic Disease of CAS, Innovation Center for Cell Biology, School of Life Sciences, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, China.
authors.forename: Zhenye
authors.initials: Z
authors.lastname: Yang
keywords: Aurora-A; H3T3-ph; Haspin; chromosomal passenger complex; spindle assembly checkpoint