CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.
| dc.contributor.author | Lin, Chao-Chieh | |
| dc.contributor.author | Kitagawa, Mayumi | |
| dc.contributor.author | Tang, Xiaohu | |
| dc.contributor.author | Hou, Ming-Hsin | |
| dc.contributor.author | Wu, Jianli | |
| dc.contributor.author | Qu, Dan Chen | |
| dc.contributor.author | Srinivas, Vinayaka | |
| dc.contributor.author | Liu, Xiaojing | |
| dc.contributor.author | Thompson, J Will | |
| dc.contributor.author | Mathey-Prevot, Bernard | |
| dc.contributor.author | Yao, Tso-Pang | |
| dc.contributor.author | Lee, Sang Hyun | |
| dc.contributor.author | Chi, Jen-Tsan | |
| dc.date.accessioned | 2021-02-21T12:21:47Z | |
| dc.date.available | 2021-02-21T12:21:47Z | |
| dc.date.issued | 2018-03-12 | |
| dc.date.updated | 2021-02-21T12:21:41Z | |
| dc.description.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. | |
| dc.identifier.issn | 2041-1723 | |
| dc.identifier.issn | 2041-1723 | |
| dc.identifier.uri | ||
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Nature communications | |
| dc.relation.isversionof | 10.1038/s41467-018-03422-6 | |
| dc.subject | Cell Line | |
| dc.subject | Humans | |
| dc.subject | Transferases | |
| dc.subject | Cell Cycle Proteins | |
| dc.subject | Microtubule-Associated Proteins | |
| dc.subject | Nuclear Proteins | |
| dc.subject | Mitosis | |
| dc.subject | Protein Binding | |
| dc.subject | Acetylation | |
| dc.subject | CREB-Binding Protein | |
| dc.subject | Aurora Kinase A | |
| dc.title | CoA synthase regulates mitotic fidelity via CBP-mediated acetylation. | |
| dc.type | Conference | |
| duke.contributor.orcid | Chi, Jen-Tsan|0000-0003-3433-903X | |
| pubs.begin-page | 1039 | |
| pubs.issue | 1 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Pharmacology & Cancer Biology | |
| pubs.organisational-group | Radiation Oncology | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Pediatrics, Hematology-Oncology | |
| pubs.organisational-group | Pediatrics | |
| pubs.organisational-group | Molecular Genetics and Microbiology | |
| pubs.organisational-group | Medicine, Rheumatology and Immunology | |
| pubs.organisational-group | Medicine | |
| pubs.publication-status | Published | |
| pubs.volume | 9 |
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