Bloom Celia R, North Brian J
Biomedical Sciences Department, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE, 68178, USA.
Cell Biosci. 2021 Apr 23;11(1):76. doi: 10.1186/s13578-021-00589-2.
BubR1 is an essential component of the spindle assembly checkpoint (SAC) during mitosis where it functions to prevent anaphase onset to ensure proper chromosome alignment and kinetochore-microtubule attachment. Loss or mutation of BubR1 results in aneuploidy that precedes various potential pathologies, including cancer and mosaic variegated aneuploidy (MVA). BubR1 is also progressively downregulated with age and has been shown to be directly involved in the aging process through suppression of cellular senescence. Post-translational modifications, including but not limited to phosphorylation, acetylation, and ubiquitination, play a critical role in the temporal and spatial regulation of BubR1 function. In this review, we discuss the currently characterized post-translational modifications to BubR1, the enzymes involved, and the biological consequences to BubR1 functionality and implications in diseases associated with BubR1. Understanding the molecular mechanisms promoting these modifications and their roles in regulating BubR1 is important for our current understanding and future studies of BubR1 in maintaining genomic integrity as well as in aging and cancer.
BubR1是有丝分裂过程中纺锤体组装检查点（SAC）的重要组成部分，其作用是防止后期开始，以确保染色体正确排列和动粒与微管附着。BubR1的缺失或突变会导致非整倍体，这是包括癌症和镶嵌性杂合非整倍体（MVA）在内的各种潜在病理状态的先兆。BubR1也会随着年龄增长而逐渐下调，并且已被证明通过抑制细胞衰老直接参与衰老过程。翻译后修饰，包括但不限于磷酸化、乙酰化和泛素化，在BubR1功能的时空调节中起关键作用。在本综述中，我们讨论了目前已确定的BubR1的翻译后修饰、相关酶以及这些修饰对BubR1功能的生物学影响及其在与BubR1相关疾病中的意义。了解促进这些修饰的分子机制及其在调节BubR1中的作用，对于我们目前理解BubR1在维持基因组完整性以及衰老和癌症方面的作用以及未来相关研究至关重要。
