BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis
Open Access
- 30 April 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 28 (14), 2077-2089
- https://doi.org/10.1038/emboj.2009.123
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. There is a [Have you seen ...?][1] (July 2009) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2009.149Keywords
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