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
  • 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.