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CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.

Publication ,  Conference
Lin, C-C; Kitagawa, M; Tang, X; Hou, M-H; Wu, J; Qu, DC; Srinivas, V; Liu, X; Thompson, JW; Mathey-Prevot, B; Yao, T-P; Lee, SH; Chi, J-T
Published in: Nat Commun
March 12, 2018
Published version (DOI) Open Access Copy (Duke) Link to item

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.

Duke Scholars

J. Will Thompson
Author J. Will Thompson Pharmacology & Cancer Biology
Tso-Pang Yao
Author Tso-Pang Yao Pharmacology & Cancer Biology
Jen-Tsan Ashley Chi
Author Jen-Tsan Ashley Chi Molecular Genetics and Microbiology
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Published In

Nat Commun

DOI

10.1038/s41467-018-03422-6

EISSN

2041-1723

Publication Date

March 12, 2018

Volume

9

Issue

1

Start / End Page

1039

Location

England

Related Subject Headings

  • Transferases
  • Protein Binding
  • Nuclear Proteins
  • Mitosis
  • Microtubule-Associated Proteins
  • Humans
  • Cell Line
  • Cell Cycle Proteins
  • CREB-Binding Protein
  • Aurora Kinase A
 

Citation

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MLA
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Lin, C.-C., Kitagawa, M., Tang, X., Hou, M.-H., Wu, J., Qu, D. C., … Chi, J.-T. (2018). CoA synthase regulates mitotic fidelity via CBP-mediated acetylation. In Nat Commun (Vol. 9, p. 1039). England. https://doi.org/10.1038/s41467-018-03422-6
Lin, Chao-Chieh, Mayumi Kitagawa, Xiaohu Tang, Ming-Hsin Hou, Jianli Wu, Dan Chen Qu, Vinayaka Srinivas, et al. “CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.” In Nat Commun, 9:1039, 2018. https://doi.org/10.1038/s41467-018-03422-6.
Lin C-C, Kitagawa M, Tang X, Hou M-H, Wu J, Qu DC, et al. CoA synthase regulates mitotic fidelity via CBP-mediated acetylation. In: Nat Commun. 2018. p. 1039.
Lin, Chao-Chieh, et al. “CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.” Nat Commun, vol. 9, no. 1, 2018, p. 1039. Pubmed, doi:10.1038/s41467-018-03422-6.
Lin C-C, Kitagawa M, Tang X, Hou M-H, Wu J, Qu DC, Srinivas V, Liu X, Thompson JW, Mathey-Prevot B, Yao T-P, Lee SH, Chi J-T. CoA synthase regulates mitotic fidelity via CBP-mediated acetylation. Nat Commun. 2018. p. 1039.

Published In

Nat Commun

DOI

10.1038/s41467-018-03422-6

EISSN

2041-1723

Publication Date

March 12, 2018

Volume

9

Issue

1

Start / End Page

1039

Location

England

Related Subject Headings

  • Transferases
  • Protein Binding
  • Nuclear Proteins
  • Mitosis
  • Microtubule-Associated Proteins
  • Humans
  • Cell Line
  • Cell Cycle Proteins
  • CREB-Binding Protein
  • Aurora Kinase A