BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis |
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| Authors: | Eunhee Choi Hyerim Choe Jaewon Min Ji Yoon Choi Jimi Kim and Hyunsook Lee |
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| Affiliation: | Department of Biological Sciences and Institute of Molecular Biology and Genetics, College of Natural Sciences, Seoul National University, Seoul, Korea |
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| Abstract: | Regulation of BubR1 is central to the control of APC/C activity. We have found that BubR1 forms a complex with PCAF and is acetylated at lysine 250. Using mass spectrometry and acetylated BubR1-specific antibodies, we have confirmed that BubR1 acetylation occurs at prometaphase. Importantly, BubR1 acetylation was required for checkpoint function, through the inhibition of ubiquitin-dependent BubR1 degradation. BubR1 degradation began before the onset of anaphase. It was noted that the pre-anaphase degradation was regulated by BubR1 acetylation. Degradation of an acetylation-mimetic form, BubR1–K250Q, was inhibited and chromosome segregation in cells expressing BubR1–K250Q was markedly delayed. By contrast, the acetylation-deficient mutant, BubR1–K250R, was unstable, and mitosis was accelerated in BubR1–K250R-expressing cells. Furthermore, we found that APC/C–Cdc20 was responsible for BubR1 degradation during mitosis. On the basis of our collective results, we propose that the acetylation status of BubR1 is a molecular switch that converts BubR1 from an inhibitor to a substrate of the APC/C complex, thus providing an efficient way to modulate APC/C activity and mitotic timing. |
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| Keywords: | acetylation APC/C BubR1 Cdc20 spindle assembly checkpoint (SAC) |
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