CoA synthase regulates mitotic fidelity via CBP-mediated acetylation
Document Type
Article
Publication Date
12-1-2018
Abstract
© 2018 The Author(s). 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.
Publication Title
Nature Communications
Recommended Citation
Lin, C.,
Kitagawa, M.,
Tang, X.,
Hou, M.,
Wu, J.,
Qu, D.,
Srinivas, V.,
Liu, X.,
Thompson, J.,
Mathey-Prevot, B.,
Yao, T.,
Lee, S.,
&
Chi, J.
(2018).
CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.
Nature Communications,
9(1).
http://doi.org/10.1038/s41467-018-03422-6
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/8431