TSA‐induced JMJD2B downregulation is associated with cyclin B1‐dependent survivin degradation and apoptosis in LNCap cells
TSA‐induced JMJD2B downregulation is associated with cyclin B1‐dependent survivin degradation and apoptosis in LNCap cells
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DOI：
10.1002/jcb.24109
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发表时间：
2012-07
影响因子：
4
通讯作者：
Shan Zhu;Yueyang Li;Li Zhao;Pingfu Hou;Chenyan Shangguan;Ruosi Yao;Weina Zhang;Yu Zhang;
中科院分区：
文献类型：
--
作者：
Shan Zhu;Yueyang Li;Li Zhao;Pingfu Hou;Chenyan Shangguan;Ruosi Yao;Weina Zhang;Yu Zhang;
组蛋白去乙酰化酶（HDAC）抑制剂作为一类新型的抗肿瘤药物正在兴起，并且已经显示出诱导癌细胞凋亡的能力，并且已经鉴定出大量基因作为负责HDAC抑制剂诱导的凋亡的潜在效应物。然而，这些HDAC抑制剂在该过程中的机制作用在很大程度上仍然不确定。我们在这里报告，用HDAC抑制剂阿司他丁A（TSA）治疗LNCap前列腺癌细胞导致含Jumonji结构域的蛋白2B（JMJD 2B）下调。我们还发现TSA介导的LNCap细胞中生存素表达的降低部分归因于JMJD 2B表达的下调。这种作用可归因于通过抑制Cyclin B1/Cdc 2复合物介导的生存素Thr 34磷酸化促进生存素蛋白的降解。因此，JMJD 2B的敲低通过调节细胞周期蛋白B1依赖性生存素降解以增强凋亡途径来增强TSA诱导的凋亡。J.细胞。113：2375-2382，2012.© 2012 Wiley Periodicals，Inc.
Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti‐tumor agents and have manifested the ability to induce apoptosis of cancer cells, and a significant number of genes have been identified as potential effectors responsible for HDAC inhibitor‐induced apoptosis. However, the mechanistic actions of these HDAC inhibitors in this process remain largely undefined. We here report that the treatment of LNCap prostate cancer cells with HDAC inhibitor trichostatin A (TSA) resulted in downregulation of the Jumonji domain‐containing protein 2B (JMJD2B). We also found that the TSA‐mediated decrease in survivin expression in LNCap cells was partly attributable to downregulation of JMJD2B expression. This effect was attributable to the promoted degradation of survivin protein through inhibition of Cyclin B1/Cdc2 complex‐mediated survivin Thr34 phosphorylation. Consequently, knockdown of JMJD2B enhanced TSA‐induced apoptosis by regulating the Cyclin B1‐dependent survivin degradation to potentiate the apoptosis pathways. J. Cell. Biochem. 113: 2375–2382, 2012. © 2012 Wiley Periodicals, Inc.