Journal
EMBO JOURNAL
Volume 28, Issue 14, Pages 2077-2089Publisher
WILEY
DOI: 10.1038/emboj.2009.123
Keywords
acetylation; APC/C; BubR1; Cdc20; spindle assembly checkpoint (SAC)
Categories
Funding
- National Research Laboratory Programme [ROA-2008-000-20023-0]
- Biodiscovery Programme [M10601000130-06N0100]
- 21C Frontier Functional Human Genome Project [FG06-2-14]
- National Cancer Control Programme [0620070]
- KRF [KRF-2005-C00097]
- RCFC [R11-2005-009-03004-0]
- Seoul Science Fellowship
- National Research Foundation of Korea [2004-015-C00399, 02-2006-09-001-00, R11-2005-009-03004-0, 2009-0094022, 과06A1204, 2008-0059996] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 preanaphase 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. The EMBO Journal (2009) 28, 2077-2089. doi: 10.1038/emboj.2009.123; Published online 30 April 2009
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