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BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis

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dc.contributor.authorChoi, Eunhee-
dc.contributor.authorChoe, Hyerim-
dc.contributor.authorMin, Jaewon-
dc.contributor.authorChoi, Ji Yoon-
dc.contributor.authorKim, Jimi-
dc.contributor.authorLee, Hyunsook-
dc.date.accessioned2010-06-07T07:30:45Z-
dc.date.available2010-06-07T07:30:45Z-
dc.date.issued2009-07-22-
dc.identifier.citationThe EMBO Journal 28: 2077–2089en
dc.identifier.issn2077-2089-
dc.identifier.urihttp://hdl.handle.net/10371/67621-
dc.description.abstractRegulation 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.sponsorshipAll 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.isoenen
dc.publisherNature Publishing Groupen
dc.subjectAPC/Cen
dc.subjectBubR1en
dc.subjectCdc20en
dc.subjectspindle assembly checkpoint(SAC)en
dc.titleBubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosisen
dc.typeArticleen
dc.contributor.AlternativeAuthor최은희-
dc.contributor.AlternativeAuthor최혜림-
dc.contributor.AlternativeAuthor민재원-
dc.contributor.AlternativeAuthor최지윤-
dc.contributor.AlternativeAuthor김지미-
dc.contributor.AlternativeAuthor이현숙-
dc.identifier.doi10.1038/emboj.2009.123-
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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