Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea.
Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.
Exp Mol Med. 2018 Oct 22;50(10):1-12. doi: 10.1038/s12276-018-0168-0.
The brain-expressed X-linked 4 (BEX4) gene has been recently identified as a mediator of microtubule hyperacetylation through sirtuin 2 inhibition and is highly overexpressed in human cancers. However, the gain-of-function molecular mechanism of the BEX4 gene in human cancers still needs to be elucidated. This study shows that BEX4 colocalizes and interacts with Polo-like kinase 1 (PLK1) at centrosomes, spindle poles, and midbodies, particularly during mitosis. Interestingly, PLK1-mediated phosphorylation upregulates the stability of BEX4 protein, and the PLK1-BEX4 interaction allows abnormal mitotic cells to adapt to aneuploidy rather than undergo apoptotic cell death. In summary, these results suggest that the oncogenicity of BEX4 is conferred by PLK1-mediated phosphorylation, and thus, the BEX4-PLK1 interaction is a novel oncogenic signal that enables the acquisition of chromosomal aneuploidy.
脑表达的 X 连锁 4（BEX4）基因最近被鉴定为通过沉默信息调节因子 2 抑制微管乙酰化的介质，并且在人类癌症中高度过表达。然而，BEX4 基因在人类癌症中的功能获得分子机制仍需要阐明。本研究表明，BEX4 与中心体、纺锤体极和中间体的 Polo 样激酶 1（PLK1）共定位并相互作用，特别是在有丝分裂期间。有趣的是，PLK1 介导的磷酸化上调 BEX4 蛋白的稳定性，并且 PLK1-BEX4 相互作用允许异常有丝分裂细胞适应非整倍体而不是经历细胞凋亡。总之，这些结果表明 BEX4 的致癌性是由 PLK1 介导的磷酸化赋予的，因此，BEX4-PLK1 相互作用是一种新的致癌信号，使获得染色体非整倍体成为可能。
