CoA synthase regulates mitotic fidelity via CBP-mediated acetylation

Chao-Chieh Lin, Mayumi Kitagawa, Xiaohu Tang, Ming-Hsin Hou, Jianli Wu, Dan Chen Qu, Vinayaka Srinivas, Xiaojing Liu, J. Will Thompson, Bernard Mathey-Prevot, Tso-Pang Yao, Sang Hyun Lee and Jen-Tsan Chi ()
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Chao-Chieh Lin: Duke University School of Medicine
Mayumi Kitagawa: Duke-NUS Medical School
Xiaohu Tang: Michigan Technological University
Ming-Hsin Hou: National Yang-Ming University
Jianli Wu: Duke University School of Medicine
Dan Chen Qu: Duke University School of Medicine
Vinayaka Srinivas: Duke-NUS Medical School
Xiaojing Liu: Duke University School of Medicine
J. Will Thompson: Duke University School of Medicine
Bernard Mathey-Prevot: Duke University School of Medicine
Tso-Pang Yao: Duke University School of Medicine
Sang Hyun Lee: Duke-NUS Medical School
Jen-Tsan Chi: Duke University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here we present evidence that acetylation controlled by Coenzyme A synthase (COASY) and acetyltransferase CBP constitutes a novel mechanism that ensures faithful mitosis. We found that COASY knockdown triggers prolonged mitosis and multinucleation. Acetylome analysis reveals that COASY inactivation leads to hyper-acetylation of proteins associated with mitosis, including CBP and an Aurora A kinase activator, TPX2. During early mitosis, a transient CBP-mediated TPX2 acetylation is associated with TPX2 accumulation and Aurora A activation. The recruitment of COASY inhibits CBP-mediated TPX2 acetylation, promoting TPX2 degradation for mitotic exit. Consistently, we detected a stage-specific COASY–CBP–TPX2 association during mitosis. Remarkably, pharmacological and genetic inactivation of CBP effectively rescued the mitotic defects caused by COASY knockdown. Together, our findings uncover a novel mitotic regulation wherein COASY and CBP coordinate an acetylation network to enforce productive mitosis.

Date: 2018
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DOI: 10.1038/s41467-018-03422-6

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