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BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, Eunhee | - |
dc.contributor.author | Choe, Hyerim | - |
dc.contributor.author | Min, Jaewon | - |
dc.contributor.author | Choi, Ji Yoon | - |
dc.contributor.author | Kim, Jimi | - |
dc.contributor.author | Lee, Hyunsook | - |
dc.date.accessioned | 2010-06-07T07:30:45Z | - |
dc.date.available | 2010-06-07T07:30:45Z | - |
dc.date.issued | 2009-07-22 | - |
dc.identifier.citation | The EMBO Journal 28: 2077–2089 | en |
dc.identifier.issn | 2077-2089 | - |
dc.identifier.uri | https://hdl.handle.net/10371/67621 | - |
dc.description.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 ubiquitindependent 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. | en |
dc.description.sponsorship | All of the work from the laboratory of HL
was funded by the National Research Laboratory Programme (ROA- 2008-000-20023-0). This work was also supported by the Biodiscovery Programme (M10601000130-06N0100), the 21C Frontier Functional Human Genome Project (FG06-2-14), and the National Cancer Control Programme (0620070). Identification of the acetylation site was supported by KRF (KRF-2005-C00097). Imaging techniques and flow cytometric analyses were supported by the RCFC (R11-2005-009- 03004-0). EC is a recipient of Seoul Science Fellowship. | en |
dc.language.iso | en | en |
dc.publisher | Nature Publishing Group | en |
dc.subject | APC/C | en |
dc.subject | BubR1 | en |
dc.subject | Cdc20 | en |
dc.subject | spindle assembly checkpoint(SAC) | en |
dc.title | BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 최은희 | - |
dc.contributor.AlternativeAuthor | 최혜림 | - |
dc.contributor.AlternativeAuthor | 민재원 | - |
dc.contributor.AlternativeAuthor | 최지윤 | - |
dc.contributor.AlternativeAuthor | 김지미 | - |
dc.contributor.AlternativeAuthor | 이현숙 | - |
dc.identifier.doi | 10.1038/emboj.2009.123 | - |
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