Escaping the firing squad: Acetylation of BubR1 protects it from degradation in checkpoint cells

The Gurdon Institute, Cambridge, UK.
The EMBO Journal (Impact Factor: 10.43). 08/2009; 28(14):1991-3. DOI: 10.1038/emboj.2009.149
Source: PubMed


The spindle assembly checkpoint (SAC) is responsible for blocking cells in mitosis in the presence of unattached kinetochores. A substantial body of work has identified many of the players in this checkpoint and shown that they target the Cdc20 protein to prevent the ubiquitylation of cyclin B and securin by the anaphase promoting complex/cyclosome (APC/C). The exact mechanism by which the SAC restrains Cdc20, however, remains elusive but some evidence indicates that it may target Cdc20 for destruction by the APC/C. An interesting study in this issue of The EMBO Journal offers a new insight into this by showing that BubR1, a crucial effector, of the SAC, is acetylated in checkpoint-arrested cells and this modification is crucial for preventing BubR1 itself from destruction and the inactivation of the SAC.

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    • "Previously, we reported that BubR1 is acetylated by PCAF acetyltransferase at prometaphase and that the acetylated BubR1 inhibits APC/C. When checkpoint is satisfied, BubR1 is deacetylated and becomes a substrate of APC/C-Cdc20 (Choi et al., 2009; Yekezare and Pines, 2009). "
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    • "Conversely, mimicking BubR1 acetylation prevents mitotic exit. Together, these data suggest that BubR1 degradation by the APC/C is important for checkpoint inactivation (Choi et al. 2009; Yekezare and Pines 2009). However, apart from the CENP-E/BubR1 interaction , it remains unclear how these mechanisms are regulated by chromosome biorientation. "
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    ABSTRACT: The multidomain protein kinase BubR1 is a central component of the mitotic spindle assembly checkpoint (SAC), an essential self-monitoring system of the eukaryotic cell cycle that ensures the high fidelity of chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bi-oriented on the mitotic spindle. We discuss the roles of BubR1 in the SAC and the implications of BubR1-mediated interactions that protect against aneuploidy. We also describe the emerging roles of BubR1 in cellular processes that extend beyond the SAC, discuss how mice models have revealed unanticipated functions for BubR1 in the regulation of normal aging, and the potential role of BubR1 as therapeutic target for the development of innovative anticancer therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.
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