BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.Thislicensedoesnot permit commercial exploitation or the creation of derivative works without specific permission.

Regulation of BubR1 is central to the control of APC/Cactivity. We have found that BubR1 forms a complex withPCAF and is acetylated at lysine 250. Using mass spectro-metry and acetylated BubR1-specific antibodies, we haveconfirmed that BubR1 acetylation occurs at prometaphase.Importantly, BubR1 acetylation was required for check-point function, through the inhibition of ubiquitin-dependent BubR1 degradation. BubR1 degradation beganbefore 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 incells expressing BubR1–K250Q was markedly delayed.By contrast, the acetylation-deficient mutant, BubR1–K250R, was unstable, and mitosis was accelerated inBubR1–K250R-expressing cells. Furthermore, we foundthat APC/C–Cdc20 was responsible for BubR1 degradationduring mitosis. On the basis of our collective results, wepropose that the acetylation status of BubR1 is a molecularswitch that converts BubR1 from an inhibitor to a sub-strate of the APC/C complex, thus providing an efficientway 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 2009Subject Categories: proteins; cell cycleKeywords: acetylation; APC/C; BubR1; Cdc20; spindleassembly checkpoint (SAC)