Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways
Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways
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DOI：
10.1016/j.ejphar.2015.11.049
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发表时间：
2016-05-15
影响因子：
5
通讯作者：
Liu, Yanfang
中科院分区：
文献类型：
--
作者：
Wang, Chong;Chen, Jing;Liu, Yanfang
Aurora-B是一种蛋白激酶，主要在有丝分裂纺锤体与着丝粒的连接中起作用。Aurora-B的过度表达导致遗传信息的不均匀分布，产生非整倍体细胞，这是癌症的标志。组蛋白脱乙酰基酶（HDAC）是一类从组蛋白上的e-N-乙酰基赖氨酸氨基酸去除乙酰基基团的酶，允许组蛋白更紧密地包裹DNA，从而全局调节基因转录。此外，这些HDAC还可以修饰非组蛋白蛋白。HDAC的抑制是癌症治疗的有效策略。在这里，我们报告了Aurora-B和HDAC的抑制在细胞中发挥类似的肿瘤抑制作用。敲低Aurora B或抑制HDAC对细胞增殖的抑制作用相同。此外，我们发现Aurora-B和HDAC抑制的肿瘤抑制作用是由于诱导细胞周期停滞和/或凋亡。从机制上讲，我们证明了Aurora-B和HDAC可以协同调节AKT，mTOR和Notch通路。(C)2016由Elsevier B. V.出版
Aurora-B is a protein kinase that functions mainly in the attachment of the mitotic spindle to the centromere. Overexpression of Aurora-B causes unequal distribution of genetic information, creating aneuploidy cells, a hallmark of cancer. Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from a e-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly, thus globally regulating gene transcription. Additionally, these HDACs can also modify nonhistone proteins. Inhibition of HDACs is a potent strategy for cancer treatment. Here, we report that inhibition of Aurora-B and HDAC exerts similar tumor suppressive effects in cells. Knockdown of Aurora B or inhibition of HDAC achieved the same effect on repression of cell proliferation. Furthermore, we found that the tumor suppressive effect of Aurora-B and HDAC inhibition is due to the induction of cell cycle arrest and/or apoptosis. Mechanistically, we demonstrated that Aurora-B and HDAC can cooperatively regulate AKT, mTOR and Notch pathways. (C) 2016 Published by Elsevier B.V.