2. Academic Validation
  3. Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation

Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation

  • Nat Chem Biol. 2016 Apr;12(4):226-32. doi: 10.1038/nchembio.2017.
Fei Mo 1 2,  Xiaoxuan Zhuang 1 2,  Xing Liu 1 2 3 4 5,  Phil Y Yao 5,  Bo Qin 1 2 5,  Zeqi Su 5 6,  Jianye Zang 1 2 3 4,  Zhiyong Wang 1 2 3 4,  Jiancun Zhang 1 2 7,  Zhen Dou 1 2 3 4,  Changlin Tian 1 2 3 4,  Maikun Teng 1 2 3 4,  Liwen Niu 1 2 3 4,  Donald L Hill 8,  Guowei Fang 1 2,  Xia Ding 5 6,  Chuanhai Fu 1 2 3 4,  Xuebiao Yao 1 2 3 4
Affiliations

Affiliations

  • 1 Anhui Key Laboratory for Cellular Dynamics &Chemical Biology, Hefei, China.
  • 2 Laboratory for Organelle Dynamics &Plasticity Control, University of Science &Technology of China School of Life Sciences, Hefei, China.
  • 3 Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Hefei, China.
  • 4 Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei, China.
  • 5 Molecular Imaging Center, Morehouse School of Medicine, Atlanta, Georgia, USA.
  • 6 Department of Medical Cell Biology, Beijing University of Chinese Medicine, Beijing, China.
  • 7 State Key Laboratory of Respiratory Diseases, Guangzhou, China.
  • 8 Comprehensive Cancer Center, University of Alabama, Birmingham, Alabama, USA.
PMID: 26829474 DOI: 10.1038/nchembio.2017
Abstract

Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin-dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1-cyclin B activity to chromosome stability are not well understood. Here, we identified a signaling axis in which Aurora B activity is modulated by CDK1-cyclin B via the acetyltransferase TIP60 in human cell division. CDK1-cyclin B phosphorylates Ser90 of TIP60, which elicits TIP60-dependent acetylation of Aurora B and promotes accurate chromosome segregation in mitosis. Mechanistically, TIP60 acetylation of Aurora B at Lys215 protects Aurora B's activation loop from dephosphorylation by the Phosphatase PP2A to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling cascade that integrates protein phosphorylation and acetylation with cell cycle progression for maintenance of genomic stability.

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