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BubR1 激酶:防止非整倍体和早衰。

BubR1 kinase: protection against aneuploidy and premature aging.

机构信息

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford OX3 0BP, UK.

Center for Biomedical Informatics, Harvard Medical School, Harvard University. 10 Shattuck Street, Boston, MA 02115, USA.

出版信息

Trends Mol Med. 2015 Jun;21(6):364-72. doi: 10.1016/j.molmed.2015.04.003. Epub 2015 May 8.

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.

摘要

多结构域蛋白激酶 BubR1 是有丝分裂纺锤体组装检查点 (SAC) 的核心组成部分,SAC 是真核细胞周期的一个重要自我监测系统,通过延迟后期起始来确保染色体分离的高保真度,直到所有染色体都正确地在有丝分裂纺锤体上双定向。我们讨论了 BubR1 在 SAC 中的作用以及 BubR1 介导的相互作用对防止非整倍体的意义。我们还描述了 BubR1 在超越 SAC 的细胞过程中的新兴作用,讨论了小鼠模型如何揭示 BubR1 在调节正常衰老方面的预期功能,以及 BubR1 作为治疗靶点在开发创新抗癌疗法方面的潜在作用。

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