期刊
JOURNAL OF PROTEOME RESEARCH
卷 9, 期 9, 页码 4554-4564出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr100281h
关键词
acetylation; mitosis; RNA processing; cell cycle; histone deacetylase inhibitor
资金
- NIH [T32 DK07696, CA111479, CA090270, SR10RR025623, RR-P20-RR17695, DK53176, A1071130]
- Dan L. Duncan Cancer Center
- NATIONAL CANCER INSTITUTE [R01CA111479, P50CA090270, P50CA140388] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017695, S10RR025623] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI071130] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T32DK007696, R01DK053176] Funding Source: NIH RePORTER
Mitosis is a highly regulated process in which errors can lead to genomic instability, a hallmark of cancer. During this phase of the cell cycle, transcription is silent and RNA translation is inhibited. Thus, mitosis is largely driven by post-translational modification of proteins, including phosphorylation, methylation, ubiquitination, and sumoylation. Here, we show that protein acetylation is prevalent during mitosis. To identify proteins that are acetylated, we synchronized HeLa cells in early prometaphase and immunoprecipitated lysine-acetylated proteins with antiacetyl-lysine antibody. The immunoprecipitated proteins were identified by LC-ESI-MS/MS analysis. These include proteins involved in RNA translation, RNA processing, cell cycle regulation, transcription, chaperone function, DNA damage repair, metabolism, immune response, and cell structure. Immunoprecipitation followed by Western blot analyses confirmed that two RNA processing proteins, eIF4G and RNA helicase A, and several cell cycle proteins, including APC1, anillin, and NudC, were acetylated in mitosis. We further showed that acetylation of APC1 and NudC was enhanced by apicidin treatment, suggesting that their acetylation was regulated by histone deacetylase. Moreover, treating mitotic cells with apicidin or trichostatin A induced spindle abnormalities and cytokinesis failure. These studies suggest that protein acetylation/deacetylation is likely an important regulatory mechanism in mitosis.
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